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Молекулярно-генетические процессы у млекопитающих (крысы)

Журнальные статьи

1. U62187
Aleksidze N.G. The involvement of lectin pH3(40) in the thermoregulation of the rat brain // Neurochemical Journal. 2012. Vol. 6, № 4. P. 265–267.

We found neurolectin pH3(40) in the rat cerebral cortex, whose content depended on the temperature of the environment. The maximum hemagglutinating activity of this lectin was observed in the winter. In comparison with the warm months, neurolectin pH3(40) activity increased in December by a factor of 37. The specific inhibitors of neurolectin are D-glucosamine and N-acetyl-D-glucosamine. The optimum pH for neurolectin activity was in the range of pH 5.0-8.5. Neurolectin pH3(40) increased the activity of Ca2+-ATPase in ghost erythrocytes by a factor of 2.5. We believe that neurolectin pH3(40) is involved in the thermoregulation of the brain.


2. U62187
Baranova K.A. et al. The adaptive role of the CREB and NF-kappa B neuronal transcription factors in post-stress psychopathology models in rats // Neurochem. J. 2014. Vol. 8, № 1. P. 17–23.

We studied the dynamics of the activation of the CREB and NF-kappa B transcription factors in areas of the rat brain after exposure to pathogenic psycho-emotional stress in the model of endogenous depression and the model of posttraumatic stress disorder (PTSD), as well as after application of hypoxic preconditioning, which prevents the formation of anxiety-depressive pathologies in these models. The development of anxiety-depressive pathology in both models was associated with reduced (10 times lower than the control maximum) or basal levels of the activating transcription factors CREB and NF-kappa B in the hippocampus and the neocortex. However, in the hypothalamus, NF-kappa B overactivation (up to an 18-fold increase above the control level) was detected in the model of depression. Therefore the lack of activation of these factors in the extra-hypothalamic areas of the brain may be a common component of the pathogenesis of both depression and PTSD, while NF-kappa B overactivation in the neurosecretory centers of the hypothalamus is obviously involved in the development of depressive conditions. Antidepressant and anxiolytic actions of hypoxic preconditioning were accompanied by a mild 2- to 6-fold increase in CREB and NF-kappa B levels in the neurons of the brain in both stress paradigms. Obviously, the maintenance of optimum activity of transcription factors in the neurons of the brain plays an important role in nonspecific compensatory processes that enhance the adaptive potential of the brain under stress conditions.


3. U62187
Bashun N.Z. et al. The effect of the glycyl-proline dipeptide on the metabolism of neuroactive amino acids and indices of energy turnover in the neocortex of rats after experimental brain ischemia // Neurochem. J. 2013. Vol. 7, № 1. P. 39–44.

We studied the effects of the glycyl-proline dipeptide (Gly-Pro) at a dose of 3 mg/kg on the contents of neuroactive amino acids, including aspartate, glycine, alanine, taurine, GABA, and glutamate, the activity of the enzymes of the GABA shunt, such as GABA-transaminase, succinic semialdehyde dehydrogenase, and glutamate decarboxylase, and enzymes of glutamate metabolism, such as glutamate dehydrogenase and alanine and aspartate transaminases in the neocortex of rats subjected to 6-h brain ischemia. We used three means of dipeptide administration, including intraperitoneal, subconjunctival, and intranasal. We found that the protective anti-ischemic effect of Gly-Pro was mostly expressed after intranasal administration.


4. U62420
Baturina G.S. et al. The influence of increased NaCl uptake on the transport of Na+ and K+ across the plasma membrane of rat renal collecting duct principal cells // Dokl. Biochem. Biophys. 2013. Vol. 453, № 1. P. 280–282.

The rat posterolateral spinal fusion model with autogenic/allogenic bone graft (rat PFABG) has been increasingly utilized as an experimental model to assess the efficacy of novel fusion treatments. The objective of this study was to investigate the reliability of the rat PFABG model and examine the effects of different variables on spinal fusion. A web-based literature search from January, 1970 to September, 2015, yielded 26 studies, which included 40 rat PFABG control groups and 449 rats. Data regarding age, weight, sex, and strain of rats, graft volume, graft type, decorticated levels, surgical approach, institution, the number of control rats, fusion rate, methods of fusion assessment, and timing of fusion assessment were collected and analyzed. The primary outcome variable of interest was fusion rate, as evaluated by manual palpation. Fusion rates varied widely, from 0 to 96%. The calculated overall fusion rate was 46.1% with an I (2) value of 62.4, which indicated moderate heterogeneity. Weight > 300 g, age > 14 weeks, male rat, Sprague-Dawley strain, and autogenic coccyx grafts increased fusion rates with statistical significance. Additionally, an assessment time-point aeyen8 weeks had a trend towards statistical significance (p = 0.070). Multi-regression analysis demonstrated that timing of assessment and age as continuous variables, as well as sex as a categorical variable, can predict the fusion rate with R (2) = 0.82. In an inter-institution reliability analysis, the pooled overall fusion rate was 50.0% [44.8, 55.3%], with statistically significant differences among fusion outcomes at different institutions (p < 0.001 and I (2) of 72.2). Due to the heterogeneity of fusion outcomes, the reliability of the rat PFABG model was relatively limited. However, selection of adequate variables can optimize its use as a control group in studies evaluating the efficacy of novel fusion therapies.


5. Bhatt A.J. et al. Dexamethasone induces apoptosis of progenitor cells in the subventricular zone and dentate gyrus of developing rat brain // J. Neurosci. Res. 2013. Vol. 91, № 9. P. 1191–1202.

The use of dexamethasone in premature infants to prevent and/or treat bronchopulmonary dysplasia adversely affects neurocognitive development and is associated with cerebral palsy. The underlying mechanisms of these effects are multifactorial and likely include apoptosis. The objective of this study was to confirm whether dexamethasone causes apoptosis in different regions of the developing rat brain. On postnatal day 2, pups in each litter were randomly divided into the dexamethasone-treated (n=91) or vehicle-treated (n=92) groups. Rat pups in the dexamethasone group received tapering doses of dexamethasone on postnatal days 3-6 (0.5, 0.25, 0.125, and 0.06 mg/kg/day, respectively). Dexamethasone treatment significantly decreased the gain of body and brain weight and increased brain caspase-3 activity, DNA fragments, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and cleaved caspse-3-positive cells at 24 hr after treatment. Dexamethasone increased cleaved caspse-3-positive cells in the cortex, thalamus, hippocampus, cerebellum, dentate gyrus, and subventricular zone. Double-immunofluorescence studies show that progenitor cells in the subventricular zone and dentate gyrus preferentially undergo apoptosis following dexamethasone exposure. These results indicate that dexamethasone-induced apoptosis in immature cells in developing brain is one of the mechanisms of its neurodegenerative effects in newborn rats. (c) 2013 Wiley Periodicals, Inc.


6. U62187
Chen X.C. et al. Existence and characterization of Salsolinol synthase in neuronal cells and rat brain // Neurochem. J. 2013. Vol. 7, № 3. P. 192–197.

Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline), the endogenous dopamine-derived catechol isoquinolines whose structure is similar with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), may be a possible candidate of dopaminergic neurotoxins to elicit Parkinson's disease (PD). Catechol isoquinolines can selectively target dopaminergic neurons, leading to dopaminergic neuronal death. However, the formation and nosogenesis of these toxins remains unclear. Salsolinol synthase is a novel enzyme which condensate dopamine and acetaldehyde to salsolinol. It is the first key enzyme in the metabolic pathway of catechol isoquinolines which directly affects salsolinol and its derivative metabolism in vivo. It is also one kind of Pictet-Spenglerase, which has been little studied and need more characterization. PC12 cells and rat brains were performed to illustrate the existence of salsolinol synthase in our study. The results indicate that salsolinol synthase is a low molecular weight protein, showing enhanced activity with increase in dopamine concentration. It is suggested that salsolinol synthase is sensitive to strong acid and stable to high-temperature. In this research, existence of salsolinol synthase was confirmed in vivo, and also provided some new evidences to elucidate the endogenous catechol isoquinoline neurotoxin substances involved in the pathogenesis of PD.


7. U04533
Dalio F.M. et al. Acute cocaine treatment increases thimet oligopeptidase in the striatum of rat brain // Biochem. Biophys. Res. Commun. 2012. Vol. 419, № 4. P. 724–727.

Many studies indicate that thimet oligopeptidase (EC3.4.24.15; TOP) can be implicated in the metabolism of bioactive peptides, including dynorphin 1-8, alpha-neoendorphin, beta-neoendorphin and GnRH. Furthermore, the higher levels of this peptidase are found in neuroendocrine tissue and testis. In the present study, we have evaluated the effect of acute cocaine administration in male rats on TOP specific activity and mRNA levels in prosencephalic brain areas related with the reward circuitry; ventral striatum, hippocampus, and frontal cortex. No significant differences on TOP specific activity were detected in the hippocampus and frontal cortex of cocaine treated animals compared to control vehicle group. However, a significant increase in activity was observed in the ventral striatum of cocaine treated-rats. The increase occurred in both, TOP specific activity and TOP relative mRNA amount determined by real time RT-PCR. As TOP can be implicated in the processing of many neuropeptides, and previous studies have shown that cocaine also alters the gene expression of proenkephalin and prodynorphin in the striatum, the present findings suggest that TOP changes in the brain could play important role in the balance of neuropeptide level correlated with cocaine effects. (C) 2012 Elsevier Inc. All rights reserved.


8. U62187
Dobrotvorskaya I.S. et al. Characteristics of Oxidative Stress in Experimental Rat Brain Ischemia Aggravated by Homocysteic Acid // Neurochemical Journal. 2011. Vol. 5, № 1. P. 42–46.

We developed a new experimental model of oxidative stress in rats, which combines the effects of 3-vessel brain ischemia and an increased level of homocysteine in blood circulation. We compared the protective effects of two compounds, the agonist of cannabinoid receptors Win5521-2 and the natural antioxidant carnosine. We found that Win5521-2 has a protective effect only at a normal blood level of homocysteine, whereas carnosine is also effective under conditions of elevated homocysteine level.


9. Du Q. et al. Dairy fat blends high in alpha-linolenic acid are superior to n-3 fatty-acid-enriched palm oil blends for increasing DHA levels in the brains of young rats // J. Nutr. Biochem. 2012. Vol. 23, № 12. P. 1573–1582.

Achieving an appropriate docosahexaenoic acid (DHA) status in the neonatal brain is an important goal of neonatal nutrition. We evaluated how different dietary fat matrices improved DHA content in the brains of both male and female rats. Forty rats of each gender were born from dams fed over gestation and lactation with a low a-linolenic acid (ALA) diet (0.4% of fatty acids) and subjected for 6 weeks after weaning to a palm oil blend-based diet (10% by weight) that provided either 1.5% ALA or 1.5% ALA and 0.12% DHA with 0.4% arachidonic acid or to an anhydrous dairy fat blend that provided 1.5% or 2.3% ALA. Fatty acids in the plasma, red blood cells (RBCs) and whole brain were determined by gas chromatography. The 1.5% ALA dairy fat was superior to both the 1.5% ALA palm oil blends for increasing brain DHA (14.4% increase, P<.05). and the 2.3% ALA dairy blend exhibited a further increase that could be ascribed to both an ALA increase and n-6/n-3 ratio decrease. Females had significantly higher brain DHA due to a gender-to-diet interaction, with dairy fats attenuating the gender effect. Brain DHA was predicted with a better accuracy by some plasma and RBC fatty acids when used in combination (R-2 of 0.6) than when used individually (R-2=0.47 for RBC n-3 docosapentaenoic acid at best). In conclusion, dairy fat blends enriched with ALA appear to be an interesting strategy for achieving optimal DHA levels in the brain of postweaning rats. Human applications are worth considering. (C) 2012 Elsevier Inc. All rights reserved.


10. U15453
El-Kasaby A. et al. A Cytosolic Relay of Heat Shock Proteins HSP70-1A and HSP90 beta Monitors the Folding Trajectory of the Serotonin Transporter // J. Biol. Chem. 2014. Vol. 289, № 42. P. 28987–29000.

Mutations in the C terminus of the serotonin transporter (SERT) disrupt folding and export from the endoplasmic reticulum. Here we examined the hypothesis that a cytosolic heat shock protein relay was recruited to the C terminus to assist folding of SERT. This conjecture was verified by the following observations. (i) The proximal portion of the SERT C terminus conforms to a canonical binding site for DnaK/heat shock protein of 70 kDa (HSP70). A peptide covering this segment stimulated ATPase activity of purified HSP70-1A. (ii) A GST fusion protein comprising the C terminus of SERT pulled down HSP70-1A. The interaction between HSP70-1A and SERT was visualized in live cells by Forster resonance energy transfer: it was restricted to endoplasmic reticulum-resident transporters and enhanced by an inhibitor that traps HSP70-1A in its closed state. (iv) Co-immunoprecipitation confirmed complex formation of SERT with HSP70-1A and HSP90 beta. Consistent with an HSP relay, co-chaperones (e.g. HSC70-HSP90-organizing protein) were co-immunoprecipitated with the stalled mutants SERT-R607A/I608A and SERT-P601A/G602A. (v) Depletion of HSP90 beta by siRNA or its inhibition increased the cell surface expression of wild type SERT and SERT-F604Q. In contrast, SERT-R607A/I608A and SERT-P601A/G602A were only rendered susceptible to inhibition of HSP70 and HSP90 by concomitant pharmacochaperoning with noribogaine. (vi) In JAR cells, inhibition of HSP90 also increased the levels of SERT, indicating that endogenously expressed transporter was also susceptible to control by HSP90 beta. These findings support the concept that the folding trajectory of SERT is sampled by a cytoplasmic chaperone relay.


11. U62187
Fedotova Y.O., Pivina S.G., Ordyan N.E. Involvement of the 5-HT1A and 5-HT2A/2C serotonin receptors in the anxious behavior of prenatally stressed ovariectomized rats // Neurochem. J. 2012. Vol. 6, № 4. P. 307–310.

We compared the effects of an antagonist of 5-HT1A receptors, NAN-190 (0.1 mg/kg intraperitoneally), and an antagonist of 5-HT2A/2C receptors, ketanserin (0.1 mg/kg intraperitoneally), which were chronically injected for 14 days, on the anxiety level in prenatally stressed female rats with an ovariectomyinduced experimental deficiency of estrogens. Chronic administration of ketanserin to ovariectomized prenatally stressed females had an anxiolytic effect and corrected disturbed levels of follitropin, lutropin, and estradiol. Administration of NAN-190 to ovariectomized prenatally stressed rats increased the anxiety level and decreased the ratio between the levels of tropic and peripheral sex hormones.


12. U62187
Fominykh V.V. et al. Enzyme immunoassay for detection of protein-bound nitrotyrosine in brain tissue and cerebrospinal fluid: Methodological issues // Neurochem. J. 2012. Vol. 6, № 3. P. 239–245.

Protein-bound nitrotyrosine is a standard marker of nitrosative stress in vivo, its levels being associated with severity of nitrosative stress in neurological diseases. Using two commercially available antibodies we have developed protocols for an indirect competitive enzyme-linked immunosorbent assay (ELISA) aimed at detecting protein-bound nitrotyrosine. The working concentration range of the assay is 0.094-4 mu g/mL, the lowest limit of detection 0.063 mu g/mL, IC50 0.538 mu g/mL. In a pilot study protein-bound nitrotyrosine levels in cerebrospinal fluid of acute stroke patients and in brain tissue of rats after focal ischemia were evaluated.


13. Guan J. et al. Bone morphogenetic protein-7 (BMP-7) mediates ischemic preconditioning-induced ischemic tolerance via attenuating apoptosis in rat brain // Biochem. Biophys. Res. Commun. 2013. Vol. 441, № 3. P. 560–566.

A mild cerebral ischemic insult, also known as ischemic preconditioning (IPC), confers transient tolerance to a subsequent ischemic challenge in the brain. This study was conducted to investigate whether bone morphogenetic protein-7 (BMP-7) is involved in neuroprotection elicited by IPC in a rat model of ischemia. Ischemic tolerance was induced in rats by IPC (15 min middle cerebral artery occlusion, MCAO) at 48 h before lethal ischemia (2 h MCAO). The present data showed that IPC increased BMP-7 mRNA and protein expression after 24 h reperfusion following ischemia in the brain. In rats of ischemia, IPC-induced reduction of cerebral infarct volume and improvement of neuronal morphology were attenuated when BMP-7 was inhibited either by antagonist noggin or short interfering RNA (siRNA) pre-treatment. Besides, cerebral IPC-induced up-regulation of B-cell lymphoma 2 (Bcl-2) and down-regulation of cleaved caspase-3 at 24 h after ischemia/reperfusion (I/R) injury were reversed via inhibition of BMP-7. These findings indicate that BMP-7 mediates IPC-induced tolerance to cerebral I/R, probably through inhibition of apoptosis. (C) 2013 Elsevier Inc. All rights reserved.


14. Higo S. et al. Acute Graft-Versus-Host Disease of the Kidney in Allogeneic Rat Bone Marrow Transplantation // Plos One. 2014. Vol. 9, № 12. P. e115399.

Allogeneic hematopoietic cell or bone marrow transplantation (BMT) causes graft-versus- host-disease (GVHD). However, the involvement of the kidney in acute GVHD is not well-understood. Acute GVHD was induced in Lewis rats (RT1(l)) by transplantation of Dark Agouti (DA) rat (RT1(a)) bone marrow cells (6.0x10(7) cells) without immunosuppression after lethal irradiation (10 Gy). We examined the impact of acute GVHD on the kidney in allogeneic BMT rats and compared them with those in Lewis-to-Lewis syngeneic BMT control and non-BMT control rats. In syngeneic BMT and non-BMT control rats, acute GVHD did not develop by day 28. In allogeneic BMT rats, severe acute GVHD developed at 21-28 days after BMT in the skin, intestine, and liver with decreased body weight (> 20%), skin rush, diarrhea, and liver dysfunction. In the kidney, infiltration of donor-type leukocytes was by day 28. Mild inflammation characterized by infiltration of CD3+ T-cells, including CD8+ T-cells and CD4+ T-cells, and CD68+ macrophages to the interstitium around the small arteries was noted. During moderate to severe inflammation, these infiltrating cells expanded into the peritubular interstitium with peritubular capillaritis, tubulitis, acute glomerulitis, and endarteritis. Renal dysfunction also developed, and the serum blood urea nitrogen (33.9 +/- 4.7 mg/dL) and urinary N-acetyl-beta-D-glucosaminidase (NAG: 31.5 +/- 15.5 U/L) levels increased. No immunoglobulin and complement deposition was detected in the kidney. In conclusion, the kidney was a primary target organ of acute GVHD after BMT. Acute GVHD of the kidney was characterized by increased levels of urinary NAG and cell-mediated injury to the renal microvasculature and renal tubules.


15. Holmqvist S. et al. Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats // Acta Neuropathol. 2014. Vol. 128, № 6. P. 805–820.

The cellular hallmarks of Parkinson's disease (PD) are the loss of nigral dopaminergic neurons and the formation of alpha-synuclein-enriched Lewy bodies and Lewy neurites in the remaining neurons. Based on the topographic distribution of Lewy bodies established after autopsy of brains from PD patients, Braak and coworkers hypothesized that Lewy pathology primes in the enteric nervous system and spreads to the brain, suggesting an active retrograde transport of alpha-synuclein (the key protein component in Lewy bodies), via the vagal nerve. This hypothesis, however, has not been tested experimentally thus far. Here, we use a human PD brain lysate containing different forms of alpha-synuclein (monomeric, oligomeric and fibrillar), and recombinant alpha-synuclein in an in vivo animal model to test this hypothesis. We demonstrate that alpha-synuclein present in the human PD brain lysate and distinct recombinant alpha-synuclein forms are transported via the vagal nerve and reach the dorsal motor nucleus of the vagus in the brainstem in a time-dependent manner after injection into the intestinal wall. Using live cell imaging in a differentiated neuroblastoma cell line, we determine that both slow and fast components of axonal transport are involved in the transport of aggregated alpha-synuclein. In conclusion, we here provide the first experimental evidence that different alpha-synuclein forms can propagate from the gut to the brain, and that microtubule-associated transport is involved in the translocation of aggregated alpha-synuclein in neurons.


16. U04533
Kang R., Zhang J. A natural squamosamide derivative FLZ inhibits homocysteine-induced rat brain microvascular endothelial cells dysfunction // Biochem. Biophys. Res. Commun. 2012. Vol. 417, № 4. P. 1176–1181.

Hyperhomocysteinemia is believed to induce endothelial dysfunction, which is an independent risk factor for atherosclerosis and vascular diseases. Compound FLZ is a novel synthetic squamosamide cyclic analog with several phenolic hydroxy groups, and exhibits strong anti-oxidative and neuroprotective activities in Alzheimer's and Parkinson's models. In the present study, we examined the actions of FLZ against homocysteine-induced injury to primary cultured rat brain microvascular endothelial cell (rBMECs). Cell survival was measured by MTT assay. Cell nuclei were observed by Hoechst 33342 staining. Senescent cells were detected by senescence-associated p-galactosidase (SA-beta-gal) staining. Reactive oxygen species (ROS) were measured by 2 ',7 '-dichlorofluorescein (DCF) fluorescent microscopy. Homocysteine-induced expression of NF-kappa B, p53, Noxa and Fas, and the release of mitochondrial cytochrome c, were measured by Western blotting. We found that FLZ treatment antagonized homocysteine-induced cell death and apoptosis and increased numbers of senescent cells. These changes were correlated with decreased ROS accumulation. FLZ treatment inhibited activation of NF-kappa B, the upregulation of p53, Noxa, and Fas, and blocked mitochondrial cytochrome c release. These data suggest that FLZ has a protective action against homocysteine-induced toxicity in rBMECs, suggesting that FLZ may have therapeutic potential for the prevention of cardiovascular diseases. (C) 2011 Elsevier Inc. All rights reserved.


17. U62187
Khalilov R.A. et al. Analysis of the kinetic characteristics of lactate dehydrogenase from the rat brain during ischemia and reperfusion // Neurochem. J. 2014. Vol. 8, № 4. P. 265–270.

We studied the activity and kinetic characteristics of lactate dehydrogenase (LDH) during partial global ischemia and reperfusion of rat brain. We found that occlusion of carotid arteries for 1 hour results in an increase in the LDH activity within the entire range of pyruvate concentrations that we used in our study. The character of the concentration dependence of the enzyme activity did not change and K (i) for the area of inhibition by pyruvate excess did not significantly increase. The increase in the efficacy of LDH catalysis during ischemia is determined by an increase in V (max) associated with an insignificant decrease in K (m). During postischemic brain reperfusion, LDH activity at all studied pyruvate concentrations decreased. The optimum point on the plot of concentration dependence shifts to the area of higher pyruvate concentrations, which is related to a decrease in K (i). A dramatic decrease in the efficacy of catalysis is determined by a considerable increase in K (m) and a decrease in V (max). Possible mechanisms of changes in the activity and kinetic characteristics of LDH during ischemia and reperfusion of the brain are discussed.


18. U62187
Khlebnikova N.N. et al. The effects of imipramine and the inhibitor of prolylendopeptidase benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine on the levels of monoamines and their metabolites in the brain of rats with an experimental anxious-depressive state // Neurochem. J. 2014. Vol. 8, № 4. P. 271–276.

Using a model of the anxious-depressive state in rats induced by postnatal administration of the inhibitor of dipeptidylpeptidase-IV, methionyl-2(S)-cyanopyrrolidine, we revealed an increase in the metabolism of 5-OTP (which was evaluated using the 5-OIAA/5-OTP ratio) in the frontal cortex. In addition, we found a decrease in DA metabolism in the hypothalamus, which was seen as a decrease in levels of the HVA and (DOPAC + HVA)/DA ratio, and a decrease in the DA content in the hippocampus. A 10-day administration of the tricyclic antidepressant imipramine at a dose of 10 mg/kg or a non-competitive inhibitor of prolylendopeptidase, benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine, at a dose of 2 mg/kg prevented the development of depressive symptoms and alterations of monoamines and their metabolism in the rat brain.


19. U04533
Kim H.R. et al. Direct detection of tetrahydrobiopterin (BH4) and dopamine in rat brain using liquid chromatography coupled electrospray tandem mass spectrometry // Biochem. Biophys. Res. Commun. 2012. Vol. 419, № 4. P. 632–637.

A simple and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of tetrahydrobiopterin (BH4) and dopamine in rat brain using epsilon-acetamidocaproic acid (AACA) as an internal standard. Proteins in the samples were precipitated with acetonitrile and then the supernatants were separated by a Sepax Polar-Imidazole (2.1 x 100 mm, i.d., 3 mu m) column using a mixture of 10 mM ammonium formate in acetonitrile/water (75:25, v/v) as the mobile phase at a flow rate of 300 mu l/min. Quantification was performed on a triple quadrupole mass spectrometer employing electrospray ionization with the operating conditions as multiple reaction monitoring (MRM) and positive ion mode from m/z 242.1 -> 166.0 for BH4, m/z 154.1 -> 90.0 for dopamine and m/z 174.1 -> 114.0 for AACA (IS). The total chromatographic run time was for 5.5 min. The method was validated for the analysis of samples: the limit of detection was 10 ng/g. The calibration curve was linear between 10-2000 ng/g for BH4 (r(2) = 0.995) and 10-5000 ng/g for dopamine (r(2) = 0.997) in the rat brain. Thus, good correlated LC-ESI/MS/MS results were obtained and found to be a powerful tool for the quantitative analysis of BH4 and dopamine in the rat brain. (C) 2012 Elsevier Inc. All rights reserved.


20. U01978
Kinoshita K., Jingu S., Yamaguchi J. A surrogate analyte method to determine D-serine in mouse brain using liquid chromatography-tandem mass spectrometry // Anal. Biochem. 2013. Vol. 432, № 2. P. 124–130.

A bioanalytical method for determining endogenous D-serine levels in the mouse brain using a surrogate analyte and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. [2,3,3-H-2]D-serine and [N-15]D-serine were used as a surrogate analyte and an internal standard, respectively. The surrogate analyte was spiked into brain homogenate to yield calibration standards and quality control (QC) samples. Both endogenous and surrogate analytes were extracted using protein precipitation followed by solid phase extraction. Enantiomeric separation was achieved on a chiral crown ether column with an analysis time of only 6 min without any derivatization. The column eluent was introduced into an electrospray interface of a triple-quadrupole mass spectrometer. The calibration range was 1.00 to 300 nmol/g, and the method showed acceptable accuracy and precision at all QC concentration levels from a validation point of view. In addition, the brain o-serine levels of normal mice determined using this method were the same as those obtained by a standard addition method, which is time-consuming but is often used for the accurate measurement of endogenous substances. Thus, this surrogate analyte method should be applicable to the measurement of D-serine levels as a potential biomarker for monitoring certain effects of drug candidates on the central nervous system. (C) 2012 Elsevier Inc. All rights reserved.


21. U62187
Kushnareva E.Y. et al. The Levels of Monoamines and their Metabolites in the Brain Structures of Rats with an Experimental Anxiodepressive State Induced by Administration of an Inhibitor of Dipeptidyl Peptidase 4 in the Early Postnatal Period // Neurochem. J. 2012. Vol. 6, № 1. P. 29–37.

Thalamic neurons receive inputs from cortex and their responses are modulated by the basal ganglia (BG). This modulation is necessary to properly relay cortical inputs back to cortex and downstream to the brain stem when movements are planned. In Parkinson's disease (PD), the BG input to thalamus becomes pathological and relay of motor-related cortical inputs is compromised, thereby impairing movements. However, high frequency (HF) deep brain stimulation (DBS) may be used to restore relay reliability, thereby restoring movements in PD patients. Although therapeutic, HF stimulation consumes significant power forcing surgical battery replacements, and may cause adverse side effects. Here, we used a biophysical-based model of the BG-Thalamus motor loop in both healthy and PD conditions to assess whether low frequency stimulation can suppress pathological activity in PD and enable the thalamus to reliably relay movement-related cortical inputs. We administered periodic pulse train DBS waveforms to the sub-thalamic nucleus (STN) with frequencies ranging from 0-140 Hz, and computed statistics that quantified pathological bursting, oscillations, and synchronization in the BG as well as thalamic relay of cortical inputs. We found that none of the frequencies suppressed all pathological activity in BG, though the HF waveforms recovered thalamic reliability. Our rigorous study, however, led us to a novel DBS strategy involving low frequency multi-input phase-shifted DBS, which successfully suppressed pathological symptoms in all BG nuclei and enabled reliable thalamic relay. The neural restoration remained robust to changes in the model parameters characterizing early to late PD stages.


22. U04533
Lee S., Kim J., Choi S. In vitro synaptic reconsolidation in amygdala slices prepared from rat brains // Biochem. Biophys. Res. Commun. 2011. Vol. 407, № 2. P. 339–342.

We compared the effects of an antagonist of 5-HT1A receptors, NAN-190 (0.1 mg/kg intraperitoneally), and an antagonist of 5-HT2A/2C receptors, ketanserin (0.1 mg/kg intraperitoneally), which were chronically injected for 14 days, on the anxiety level in prenatally stressed female rats with an ovariectomyinduced experimental deficiency of estrogens. Chronic administration of ketanserin to ovariectomized prenatally stressed females had an anxiolytic effect and corrected disturbed levels of follitropin, lutropin, and estradiol. Administration of NAN-190 to ovariectomized prenatally stressed rats increased the anxiety level and decreased the ratio between the levels of tropic and peripheral sex hormones.


23. Lin H. et al. Effect of Mixed Transplantation of Autologous and Allogeneic Microskin Grafts on Wound Healing in a Rat Model of Acute Skin Defect // Plos One. 2014. Vol. 9, № 1. P. e85672.

The treatment of extensive thermal injuries with insufficient autologous skin remains a great challenge to burn surgeons. In this study, we investigated the influence of the ratio of autologous and allogeneic tissue in mixed microskin grafts on wound healing in order to develop an effective method for using limited donor skin to cover a large open wound. Four different mixtures were tested: autologous microskin at an area expansion ratio of 10:1 with allogeneic microskin at an area expansion ratio of 10:1 or 10:3 and autologous microskin at an expansion ratio of 20:1 with allogeneic microskin at an expansion ratio of 20:3 or 20:6. Wound healing, wound contraction, and integrin beta 1 expression were measured. Mixed microskin grafting facilitated wound healing substantially. The mixture of autologous microskin at an expansion ratio of 10:1 with the same amount of allogeneic microskin achieved the most satisfactory wound healing among the 4 tested mixtures. Histological examination revealed the presence of obviously thickened epidermis and ectopic integrin beta 1 expression. Keratinocytes expressing integrin beta 1 were scattered in the suprabasal layer. Higher levels of integrin beta 1 expression were associated with faster wound healing, implying that ectopic expression of integrin beta 1 in keratinocytes may play a pivotal role in wound healing. In conclusion, this study proves that this new skin grafting technique may improve wound healing.


24. Liu C. et al. DEHP reduces thyroid hormones via interacting with hormone synthesis-related proteins, deiodinases, transthyretin, receptors, and hepatic enzymes in rats // Environ. Sci. Pollut. Res. 2015. Vol. 22, № 16. P. 12711–12719.

Di-(2-ethylhexyl) phthalate (DEHP) is used extensively in many personal care and consumer products, resulting in widespread nonoccupational human exposure through multiple routes and media. Limited studies suggest that exposure to DEHP may be associated with altered thyroid function, but detailed mechanisms are unclear. In order to elucidate potential mechanisms by which DEHP disturbs thyroid hormone homeostasis, Sprague-Dawley (SD) rats were dosed with DEHP by gavage at 0, 250, 500, and 750 mg/kg/day for 30 days and sacrificed within 24 h after the last dose. Gene expressions of thyroid hormone receptors, deiodinases, transthyretin, and hepatic enzymes were measured by RTPCR; protein levels of transthyretin were also analyzed by Western blot. Results showed that DEHP caused histological changes in the thyroid and follicular epithelial cell hypertrophy and hyperplasia were observed. DEHP significantly reduced thyroid hormones (T3, T4) and thyrotropin releasing hormone (TRH) levels, whereas thyroid stimulating hormone (TSH) was not affected. After exposure to DEHP, biosynthesis of thyroid hormones was suppressed, and sodium iodide symporter (NIS) and thyroid peroxidase (TPO) levels were significantly reduced. Additionally, levels of deiodinases and transthyretin were also affected. TSH receptor (TSHr) level was downregulated, while TRH receptor (TRHr) level was upregulated. Metabolism of thyroid hormones was accelerated due to elevated gene expression of hepatic enzymes (UDPGTs and CYP2B1) by DEHP. Taken together, observed findings indicate that DEHP could reduce thyroid hormones through influencing biosynthesis, biotransformation, biotransport, receptor levels, and metabolism of thyroid hormones.


25. U62882
Liu P. et al. Morphology, mitochondrial development and adipogenic-related genes expression during adipocytes differentiation in grass carp (Ctenopharyngodon idellus) // Sci. Bull. 2015. Vol. 60, № 14. P. 1241–1251.

To investigate the differentiation mechanism of grass carp preadipocytes, a primary adipocytes culture system was established. Confluent preadipocytes were induced to differentiation, and the morphology and gene expression were evaluated at different stages. It was shown that preadipocytes were gradually filled with droplets and the cellular lipid content increased during the differentiation. Ultrastructure observation indicated that the number of mitochondria increased with adipocytes differentiation. Consistently, the mitochondrial protein content was elevated in the differentiating adipocytes. qRT-PCR showed that the expression level of lipogenesis-related genes such as peroxisome proliferator activator receptor gamma (PPAR gamma), lipoprotein lipase (LPL), fatty acid synthase (FAS) and stearoyl-CoA desaturase (SCD) increased during adipocytes differentiation. The mitochondrial relevant gene also elevated when adipocyte differentiation, such as PPAR coactivator-1 (PGC-1 alpha), PGC-1 beta and nuclear respiratory factor (NRF-1). However, the expression of carnitine palmitoyltransferase I alpha (CPT-1 alpha) gene decreased at the initial stage, but increased at the last stage of cell differentiation. These results indicated that the differentiation process of grass carp preadipocytes is similar to that of land animals, but the molecular mechanisms are not exactly the same. The findings revealed in this study provides new information to the study of fish adipocyte differentiation.


26. Lowes D.A. et al. Brief isoflurane anaesthesia affects differential gene expression, gene ontology and gene networks in rat brain // Behav. Brain Res. 2017. Vol. 317. P. 453–460.

Much is still unknown about the mechanisms of effects of even brief anaesthesia on the brain and previous studies have simply compared differential expression profiles with and without anaesthesia. We hypothesised that network analysis, in addition to the traditional differential gene expression and ontology analysis, would enable identification of the effects of anaesthesia on interactions between genes. Rats (n = 10 per group) were randomised to anaesthesia with isoflurane in oxygen or oxygen only for 15 min, and 6 h later brains were removed. Differential gene expression and gene ontology analysis of micro-array data was performed. Standard clustering techniques and principal component analysis with Bayesian rules were used along with social network analysis methods, to quantitatively model and describe the gene networks. Anaesthesia had marked effects on genes in the brain with differential regulation of 416 probe sets by at least 2 fold. Gene ontology analysis showed 23 genes were functionally related to the anaesthesia and of these, 12 were involved with neurotransmitter release, transport and secretion. Gene network analysis revealed much greater connectivity in genes from brains from anaesthetised rats compared to controls. Other importance measures were also altered after anaesthesia; median [range] closeness centrality (shortest path) was lower in anaesthetized animals (0.07 [0-0.30]) than controls (039 [0.30-0.53], p < 0.0001) and betweenness centrality was higher (53.85 132.56-70.00]% compared to 5.93 [0-30.65]%, p < 0.0001). Simply studying the actions of individual components does not fully describe dynamic and complex systems. Network analysis allows insight into the interactions between genes after anaesthesia and suggests future targets for investigation. (C) 2016 Elsevier B.V. All rights reserved.


27. U62187
Mamalyga M.L. Monoamine Metabolism in the Brain of Rats with Chronic Heart Failure of Non-Ischemic Origin // Neurochem. J. 2012. Vol. 6, № 1. P. 38–43.

Chronic heart failure (CHF) modulates the activity of monoaminergic systems in the central nervous system (CNS). An increased dioxyphenylacetic acid/dopamine ratio and 5-oxyindoleacetic acid/serotonin ratio in the majority of the brain structures studied during CHF indicate the high activity of the dopamine and serotonin systems and their functional stress during the development of hypoxia-compensative processes aimed at the maintenance of the normal cerebral blood flow. However, if a convulsive seizure develops during CHF, it may result in the failure of compensatory and adaptive mechanisms, thus, leading to decreased levels of dopamine, serotonin, and their metabolites in most brain regions studied. These animals are also characterized by increased seizure readiness, which is not usually found in the postictal period in rats without heart pathologies. Hence, CHF prolongs the postictal changes in the brain, limits its capacity to recovery, which, in turn, builds a basis for further seizure development.


28. U62187
Manzhulo I.V. et al. The specific response of neurons and glial cells of the ventromedial reticular formation in the rat brainstem to acute pain // Neurochem. J. 2013. Vol. 7, № 1. P. 62–68.

We studied the time course of changes in neurochemical modifications in neurons and glial cells of the ventromedial reticular formation of the rat brainstem during the development of acute inflammatory pain. The development of the pain response was associated with a twofold increase in the number of neurons that expressed NADPH diaphorase in the ventromedial reticular formation as compared to the norm. At 2 hours after the development of the pain response, we observed an increase in the number of tyrosine hydroxylase-positive elements, which was 1.5 times higher as compared to the norm. The development of acute pain was also associated with a glial response in the nucleus: the activity of mature astrocytes increased by a factor of 1.9 whereas the area of immunohistochemically stained microglia decreased by a factor of 7.6 compared to the norm. The results of our study demonstrate that development of the acute-pain response is related to the activation of both neurons and glial cells of the ventromedial nucleus of the reticular formation.


29. Martin J.V. et al. Effects of acute microinjections of thyroid hormone to the preoptic region of euthyroid adult male rats on sleep and motor activity // Brain Res. 2013. Vol. 1516. P. 45–54.

In adult brain tissue, thyroid hormones are known to have multiple effects which are not mediated by chronic influences of the hormones on heterodimeric thyroid hormone nuclear receptors. Previous work has shown that acute microinjections of L-triiodothyronine (T3) to the preoptic region significantly influence EEG-defined sleep in hypothyroid rats. The current study examined the effects of similar microinjections in euthyroid rats. In 7 rats with histologically confirmed microinjection sites bilaterally placed in the preoptic region, slow-wave sleep time was significantly decreased, but REM and waking were increased as compared to vehicle-injected Controls. The EEG-defined parameters were significantly influenced by the microinjections in a biphasic dose-response relationship; the lowest (0.3 mu g) and highest (10 mu g) doses tested were without significant effect while intermediate doses (1 and 3 mu g) induced significant differences from controls. There were significant diurnal variations in the measures, yet no significant interactions between the effect of hormone and time of day were demonstrated. Core body temperature was not significantly altered in the current study. The demonstration of effects of T3 within hours instead of days is consistent with a rapid mechanism of action such as a direct influence on neurotransmission. Since the T3-mediated effects were robust in the current work, euthyroid rats retain thyroid hormone sensitivity which would be needed if sleep-regulatory mechanisms in the preoptic region are continuously modulated by the hormones. This article is part of a Special Issue entitled Linked: BRES-D-12-01552 & BRES-D-12-01363R2. (c) 2013 Elsevier B.V. All rights reserved.


30. U62187
Matveeva M.I. et al. The effects of irradiation by C-12 carbon ions on monoamine exchange in several rat brain structures // Neurochem. J. 2013. Vol. 7, № 4. P. 303–307.

Rats were irradiated with carbon ions (C-12) in a Nuklotron accelerator. The irradiation dose was 1 Gy, the energy of the ions was 500 MeV/nuclon, and the linear energy transmission (LET) was 10.6 keV/micron. The animals were decapitated 1 day after irradiation. We isolated the prefrontal cortex, nucleus accumbens, hypothalamus, hippocampus, and striatum, where we determined the concentrations of monoamines and their metabolites. Strong changes were observed in three structures, viz., the prefrontal cortex, nucleus accumbens, and hippocampus. However, significant changes were found in the prefrontal cortex and weaker changes were seen in the nucleus accumbens, whereas changes were insignificant in the hippocampus. This reaction may be related to the fact that the animals were examined on the 2nd day after irradiation. It was shown that an increase in the interval between irradiation and examination of animals results in enhancement of the effects of radiation treatment. The experiments revealed the high sensitivity and reactivity of the prefrontal cortex, which we relate to the key role of this structure in vitally critical processes of behavior.


31. U62187
Men’shanov P.N., Muzyka V.V., Dygalo N.N. Coordinated Expression of Pro- and Antiapoptotic Proteins in the Hippocampus of Neonatal Rats // Neurochem. J. 2011. Vol. 5, № 1. P. 20–23.

We studied the contents of the apoptotic proteins Bcl-XL, Bax, and intact and active forms of caspase-3 using the immunoblot method in the hippocampus and brainstem of 3-day-old rat pups. The expression of pro- and antiapoptotic proteins in the regions of the developing brain demonstrates individual variability with a variation coefficient ranging from 10 to 40%. In the brainstem, a structure with a low intensity of apoptosis at this period of ontogeny, correlations between the expression levels of these proteins were not significant. However, in the hippocampus we observed a significant positive correlation between the levels of expression of the proapoptotic proteins Bax and the active form of caspase-3 (r = +0.653). The levels of these proteins significantly negatively correlated with the content of the antiapoptotic protein Bcl-XL (r = -0.651 and -0.740, respectively). Our data suggest coordinated expression of the apoptotic cascade proteins in the hippocampus, a brain structure with a high intensity of elimination of excessive cells during early postnatal ontogeny.

32. U62187
Muzyka V.V. et al. The interrelationship between BDNF and its precursor and the level of active caspase-3 in the brain regions of neonatal rats // Neurochem. J. 2012. Vol. 6, № 4. P. 260–264.

Brain-derived neurotrophic factor (mat-BDNF) promotes neuronal survival, whereas its precursor protein (pro-BDNF) induces cell death, which indicates the opposite but potentially important roles of both forms of this neurotrophin in brain development. We studied the contents of mat- and pro-BDNF and active caspase-3 in the brain regions of 8-day-old rat pups. Taking the level of caspase-3 in the cerebral cortex into account we may conclude that intense apoptosis occurs in this structure; however, the ratio of mat-BDNF to pro-BDNF in this region was the lowest among all structures studied. In contrast, in the brainstem of neonatal rats, where processes of cell proliferation and elimination are completed, the mat-BDNF/pro-BDNF ratio was substantially higher compared to the cortex. The mat-BDNF/pro-BDNF ratio in the cerebellum and hippocampus also supports the inverse relationship between this index and the level of active caspase-3 in different brain regions. Our data suggest that both forms of BDNF are involved in the determination of cell fate in the developing brain.


33. U04533
Nakamura K. et al. A subpopulation of endothelial progenitor cells with low aldehyde dehydrogenase activity attenuates acute ischemic brain injury in rats // Biochem. Biophys. Res. Commun. 2012. Vol. 418, № 1. P. 87–92.

Previous studies have examined the therapeutic effect of endothelial progenitor cells (EPCs) during the chronic phase of cerebral infarction in rats; however, few studies have investigated the effects of EPCs during the acute phase of infarction. In this study, we evaluated the therapeutic effect of EPCs with low aldehyde dehydrogenase activity (Aide-Low EPCs) in rats with acute cerebral infarction, and our results provide insight that may help to identify a therapeutic mechanism of EPCs for acute cerebral infarction. The administration of Alde-Low EPCs into rats with acute cerebral infarction results in the accumulation and migration of the Aide-Low EPCs into the infarct area and the subsequent decrease of infarct volume. Moreover, we found that the stromal cell-derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) signaling pathway may regulate the accumulation of Aide-Low EPCs. The transplantation of Aide-Low EPCs may represent a potential treatment strategy for acute cerebral infarction. (C) 2012 Elsevier Inc. All rights reserved.


34. Nakayama H. et al. Effect of calcitonin on adrenocorticotropic hormone secretion stimulated by corticotropin-releasing hormone in the hen anterior pituitary // Anim. Sci. J. 2011. Vol. 82, № 3. P. 475–480.

The presence of a receptor for calcitonin (CT) and the effect of chicken CT (cCT) on adrenocorticotropic hormone (ACTH) secretion stimulated by rat/human corticotropin-releasing hormone (rhCRH) in the hen anterior pituitary were studied. The specific [125I]cCT binding component was present in the plasma membrane of hen anterior pituitary and this binding component had properties of a receptor which has binding specificity to cCT, reversibility, saturable binding, high affinity and limited capacity. When anterior pituitary cells were incubated in vitro, cCT increased the maximal secretion of chicken ACTH stimulated by rhCRH. These results suggest that CT may act directly on the anterior pituitary via its receptor binding and enhances the ACTH secretion by CRH.


35. U62187
Narkevich V.B. et al. The effects of himantane and cycloprolylglycine on the enzymatic linkage of monoamine synthesis in the rat brain // Neurochemical Journal. 2012. Vol. 6, № 4. P. 272–277.

Using HPLC we studied the effects of new substances with antiparkinsonian activities, viz., himantane and cycloprolylglycine (CPG), on the contents of monoamines and their metabolites in the brain structures of Wistar rats under conditions of the inhibition of tyrosine and tryptophan hydroxylases. It was shown that 70 min after administration himantane induces a significant decrease in the level of noradrenaline in the nucleus accumbens (NA) and striatum. At 70 min after administration of CPG, we observed an increase in the DOPAC/DA ratio in the NA and the level of 5-HIAA in the striatum. At 24 h after CPG administration, we observed an increase in the HVA content and HVA/DA ratio in the hypothalamus and striatum. We found a decrease in 5-HIAA in all brain structures we studied at 24 h after administration of CPG, which was absent at 70 min after injection of the substance; the magnitude of 5-HIAA/5-HT decreased in the hypothalamus, nucleus accumbens, and hippocampus. Our results suggest that both substances we studied influence serotonergic transmission by inhibition of the MAO B enzyme.


36. U62187
Nazaryan N.S. et al. The effects of the lithium salt of GABA on the subcellular metabolic profile of L-arginine in the prefrontal cortex and striatum of rats during chronic stress // Neurochem. J. 2012. Vol. 6, № 4. P. 299–306.

Our previous data suggest that depression-like behavior of rats, which is induced by the 14-daylong unpredictable influence of stress factors, is accompanied by a sustained increase in the contents of L-arginine and nitric oxide (NO) and its stable metabolites, as well as stimulation of the inducible isoform of NO synthase (iNOS) and suppression of the activity of its constitutive NOS isoforms (cNOS) in the cytosol and mitochondria of the prefrontal cortex (PFC) and striatum. A single intraperitoneal injection of GABA lithium salt (at a dose of 0.9 mg/kg) on the second day of the post-stress period normalized the levels of L-arginine and active forms of nitrogen in cellular compartments from the PFC and striatum. Although this treatment did not influence the stress-induced shifts in the activity of cNOS, it prevented stimulation of the iNOS/NO system of mitochondria due to blockage of NO hyperproduction and nitrosative stress, whose development results in the disturbance of energetic processes in these brain areas.


37. U01978
Notarangelo F.M. et al. Gas chromatography/tandem mass spectrometry detection of extracellular kynurenine and related metabolites in normal and lesioned rat brain // Anal. Biochem. 2012. Vol. 421, № 2. P. 573–581.

We describe here a gas chromatography-tandem mass spectrometry (GC/MS/MS) method for the sensitive and concurrent determination of extracellular tryptophan and the kynurenine pathway metabolites kynurenine, 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN) in rat brain. This metabolic cascade is increasingly linked to the pathophysiology of several neurological and psychiatric diseases. Methodological refinements, including optimization of MS conditions and the addition of deuterated standards, resulted in assay linearity to the low nanomolar range. Measured in samples obtained by striatal microdialysis in vivo, basal levels of tryptophan, kynurenine, and QUIN were 415, 89, and 8 nM, respectively, but 3-HK levels were below the limit of detection (<2 nM). Systemic injection of kynurenine (100 mg/kg, i.p.) did not affect extracellular tryptophan but produced detectable levels of extracellular 3-HK (peak after 2-3 h: similar to 50 nM) and raised extracellular QUIN levels (peak after 2 h: similar to 105 nM). The effect of this treatment on QUIN, but not on 3-HK, was potentiated in the N-methyl-D-aspartate (NMDA)-lesioned striatum. Our results indicate that the novel methodology, which allowed the measurement of extracellular kynurenine and 3-HK in the brain in vivo, will facilitate studies of brain kynurenines and of the interplay between peripheral and central kynurenine pathway functions under physiological and pathological conditions. (C) 2011 Elsevier Inc. All rights reserved.


38. U62187
Onufriev M.V. et al. Neuroimmune aspects of brain damage after focal ischemia // Neurochem. J. 2014. Vol. 8, № 1. P. 71–77.

We have studied the level of products of nitrosative stress, immunoglobulins, and antibodies against nitrated proteins in the cerebrospinal fluid (CSF) and in the neocortex of rats 24 hours after focal ischemia. In the acute stage after ischemia, the level of metabolites of nitric oxide, nitrate, and nitrite, significantly increased in the CSF and in the ischemic neocortex of the animals. In addition, in the CSF of rats, the level of immunoglobulins (Ig) significantly increased and the nitrotyrosine-BSA binding was enhanced. Immunochemical staining of the sections of the brain by anti-rat Ig antibodies revealed their presence in the ischemic focus but not in the contralateral hemisphere. In the ischemic hemisphere in some Ig-positive cells, we observed colocalization of staining with the pro-apoptotic protein Bax. At this stage, in the ischemic hemisphere a membrane attack complex, the product of the terminal stage of complement activation, was detected by immunohistochemistry. Thus, the development of an immune response during the acute stage after experimental stroke is associated with some features of apoptotic cell death and seems to a certain extent to be modulated by nitrosative stress products, such as proteins modified by nitration.


39. U62187
Peregud D.I. et al. Expression of the mRNA of neurotrophins in brain regions of rats after spontaneous morphine withdrawal // Neurochem. J. 2011. Vol. 5, № 2. P. 126–132.

The expression of specific genes is an important factor of neuroplastic changes during the formation of opiate dependence. Neurotrophic factors participate in structural-functional modifications in CNS regions after opiate intoxication. Here, we studied the levels of mRNAs of the brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and insulin-like growth factor 1 (IGF1) in the frontal cortex, striatum, hippocampus, and midbrain after spontaneous morphine withdrawal in dependent rats. To induce physical dependence, morphine was injected intraperitoneally twice a day with increasing doses of 10-100 mg/kg for 6 days. The expression of mRNAs of BDNF, NGF, and IGF1 in the brain areas was estimated 40 hours after spontaneous morphine withdrawal using the real-time PCR method. We found that spontaneous morphine withdrawal induced an elevation of BDNF and IGF1 mRNAs in the frontal cortex. In the hippocampus and the midbrain only BDNF mRNA increased. The content of NGF mRNA did not change in all regions studied. We believe that changes in the expression of BDNF and IGF1 are involved in the mechanisms of neuroplastic modification during the formation of opiate dependence.


40. Romero Gonzalez R. et al. Development and validation of an ultra-high performance liquid chromatography-tandem mass-spectrometry (UHPLC-MS/MS) method for the simultaneous determination of neurotransmitters in rat brain samples // J. Neurosci. Methods. 2011. Vol. 198, № 2. P. 187–194.

A simple method for the simultaneous determination of glutamate, gamma-aminobutyric acid (GABA), choline, acetylcholine, dopamine, 5-hydroxyindole-3-acetic (5-HIAA), serotonin, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) was developed by using ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). These compounds are analysed in a single chromatographic run in less than 8 min, adding heptafluorobutyric acid (HFBA) in the mobile phase to improve the separation of the selected neurotransmitters. The analytes were detected using electrospray ionization (ESI)-MS/MS in positive mode with multiple reaction monitoring (MRM). Good linearity was obtained (R(2) > 0.98) and the intra and inter-day precision of the method (expressed as relative standard deviation) were lower than 26%. Limits of quantification were lower than 2.440 mu g/g of brain in all the cases, allowing the sensitive determination of these compounds in rat brain extracts. Therefore, the method was successfully applied for the quantitative determination of neurotransmitters in several rat brain regions (prefrontal cortex, striatum, nucleus accumbens and amygdala), detecting glutamate, GABA and choline at concentrations higher than 1000 mu g/g, 30 mu g/g and 100 mu g/g respectively, whereas the other compounds were found at lower concentrations. (C) 2011 Elsevier B.V. All rights reserved.


41. U01978
Ru Y. et al. A micropreparation of mitochondria from cells using magnetic beads with immunoaffinity // Anal. Biochem. 2012. Vol. 421, № 1. P. 219–226.

Mitochondrial preparation is a key technique in the study of mitochondria. Growing evidence has demonstrated that mitochondrial proteins are tissue or cell type dependent. Locating the proteins in the global presence of mitochondrial membranes is a primary consideration in adopting antibodies for affinity enrichment of mitochondria on a micro scale. Two proteins located on the outer membrane of mitochondria, cytochrome b5 type B (CYB5B) and synaptojanin-2-binding protein (SYNJ2BP), were selected as candidates based on a survey of databases and the literature. The polyclonal antibodies against the truncated CYB5B and SYNJ2BP exhibited specific recognition to mitochondria and wider sensitivity to several tested mouse tissues and cell lines, whereas the antibody 22-kDa translocase of the outer mitochondrial membrane (TOM22) nearly missed detection of mitochondria in the liver and responded minimally to mitochondria from H9C2 and L-02 cells. Through the affinity enrichment for cellular mitochondria using magnetic beads coated with anti-CYB5B or anti-SYNJ2BP, we found that the anti-CYB5B beads could enrich mitochondria more efficiently even on a scale of 10,000 cultured cells. For the integrity and protein components, the enriched mitochondria on anti-CYB5B were carefully examined and were accepted in further functional study. We propose that an anti-CYB5B immunomagnetic approach is feasible in the micropreparation of mitochondria from cultured cells. (C) 2011 Elsevier Inc. All rights reserved.


42. U62187
Saifetyarova J.J. et al. Endocrine Function of Dopaminergic Neurons in the Neonatal Rat Brain // Neurochem. J. 2011. Vol. 5, № 3. P. 169–175.

We tested our hypothesis that dopamine (DA) is secreted from the brain to the blood during the perinatal period of rat ontogeny when rats have no blood-brain barrier. We developed a specific pharmacological model to inhibit DA synthesis in the brain and maintain its constant level on the periphery using alpha-methyl-p-tyrosine (alpha MPT), an inhibitor of the key enzyme of DA synthesis tyrosine hydroxylase. On the basis of preliminary systemic administration of aMPT (200, 100, 80, and 50 mu g), we selected a dose of the inhibitor of 50 mu g, which excluded its effects on DA metabolism in peripheral organs. In subsequent experiments, alpha MPT was stereotaxically administered into the lateral brain ventricles of three-day-old rats at the selected dose. After this, we measured the concentration of catecholamines and metabolites using high performance liquid chromatography with electrochemical detection in the brain, Zuckerkandl's organ, kidneys, adrenals, and plasma. We found that in 4 h after administration of the inhibitor, the DA concentration decreased in the brain by 54% and in the plasma by 74%, whereas in the peripheral organs it remained unchanged. Thus, we directly showed that DA is secreted from the brain in the general blood circulation before the formation of the BBB.


43. Sawada R., Mitaku S. Biological meaning of DNA compositional biases evaluated by ratio of membrane proteins // J. Biochem. 2012. Vol. 151, № 2. P. 189–196.

Membrane spanning regions can be used as markers for studying the robustness of biologically important units of proteins against evolutionary change (R. Sawada and S. Mitaku, Genes to Cells, 2010). We carried out computational experiments of extensive DNA mutations on the assumption of constant GC content or constant codon positional nucleotide biases. Randomized sequences were evaluated by membrane protein prediction systems SOSUI and SOSUIsignal. When all amino acid sequences from the total real genomes of 538 prokaryotes were analysed, ratios of membrane proteins to all genes in the total genomes were almost constant around a ratio of 22% with a standard deviation of 1.56. When the nucleotide sequences were randomized, keeping only the GC contents constant, the ratios of membrane proteins became highly diverse with a standard deviation of 10.1. When the codon positional nucleotide biases were taken into account; however, the diverse ratios of membrane proteins converged to a value of similar to 25% with a standard deviation of 3.55. These results suggest that codon compositional biases play an important role in the evolution of prokaryotes for maintaining a constant ratio of membrane proteins. Further detailed analysis suggested that non-uniform nucleotide compositional biases at the terminal regions are the reason for the small but significant deviation.


44. U62187
Sergutina A.V., Rakhmanova V.I. The effects of L-DOPA on cytochemical indices of oxidative metabolism in the brains of rats with different levels of motor activity // Neurochem. J. 2013. Vol. 7, № 4. P. 291–295.

We studied the brains of Wistar rats with high and low levels of motor activity in the "open field" test under normal conditions and after prolonged L-DOPA administration and its withdrawal. We performed a cytochemical study of glucose-6-phosphate dehydrogenase activity in neurons of layers III and V of the sensorimotor cortex, caudate nucleus, nucleus accumbens, and hippocampus (CA3 field). We compared the alterations of the activity of glucose-6-phosphate dehydrogenase with changes in the activity of glutamate dehydrogenase under the same conditions. We found an increase in the glucose-6-phosphate dehydrogenase and glutamate dehydrogenase activities in the striatum of rats with a high level of motor activities after L-DOPA administration. The alterations of the glucose-6-phosphate dehydrogenase and glutamate dehydrogenase activities were different in the sensorimotor cortex. Cytochemical indices in the brains of these rats recovered to a normal state after L-DOPA withdrawal. In rats with a low level of motor activity, L-DOPA administration increased glucose-6-phosphate dehydrogenase activity in the striatum (nucleus accumbens). In these rats, glutamate dehydrogenase activity decreased in the striatum and increased in the hippocampus. L-DOPA withdrawal resulted in an increase in the glucose-6-phosphate dehydrogenase activity in layer V of the sensorimotor cortex and a decrease in the glutamate dehydrogenase activity in the caudate nucleus. Thus, it was shown that the response of the oxidative metabolism of the brain to the activation of the dopaminergic system depends on the traits of a animal's behavior, in particular, its motor activity.


45. U62187
Sherstnev V.V. et al. Neurogenesis and neuroapoptosis in different brain structures of adult Wistar rats // Neurochem. J. 2012. Vol. 6, № 3. P. 179–184.

In our study, which was performed with adult Wistar rats, we investigated the pecularities of neurogenesis in different brain regions known for their association with learning and memory. The number of cells positively stained for BrdU (marker of cellular proliferation) was counted at 24 hours, 15 days, and 30 days after BrdU administration in the dentate gyrus, CA1-CA4 hippocampal subfields, different areas of the cerebral cortex, and the cerebellar vermis using the immunofluorescence method. In these brain structures, we also counted the number of new cells that were double stained for neuronal (NeuN), astrocytic (GAFP), or apoptotic (ApoDNA) markers at all examined time points. It was found that in all the studied brain regions, new cells were generated and these cells further differentiated in the neurons and astrocytes. Significant inter-structure differences were found in the proliferation, differentiation, and apoptotic death of newly generated cells. The possible reasons for inconsistencies between our data on neurogenesis/apoptosis and those obtained by other researchers in adult Wistar rats are discussed.


46. U04533
Shi G.D. et al. PTEN deletion prevents ischemic brain injury by activating the mTOR signaling pathway // Biochem. Biophys. Res. Commun. 2011. Vol. 404, № 4. P. 941–945.

It is increasingly clear that the tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a negative regulator of neuronal cell survival. However, its molecular mechanisms remain poorly understood. Here we found that PTEN/mTOR is critical for controlling neuronal cell death after ischemic brain injury. Male rats were subjected to MCAO (middle cerebral artery occlusion) followed by pretreating with bpv (pit), a potent inhibitor for PTEN, or by intra-cerebroventricular infusion of PTEN siRNA. bpv (pit) significantly decreased infarct volume and reduced the number of TUNEL-positive cells. We further demonstrated that although bpv (pic) did not affect brain injury-induced mTOR protein expression, bpv (pic) prevented decrease in phosphorylation of mTOR, and the subsequent decrease in S6. Similarly, down-regulation of PTEN expression also reduced the number of TUNEL-positive cells, and increased phospho-mTOR. These data suggest that PTEN deletion prevents neuronal cell death resulting from ischemic brain injury and that its neuroprotective effects are mediated by increasing the injury-induced mTOR phosphorylation. (C) 2010 Elsevier Inc. All rights reserved.


47. U62187
Simonyan R.M. et al. Ferrihemoglobin induces the release of NADPH oxidase from brain-cell membrane tissue ex vivo: the suppression of this process by galarmin // Neurochem. J. 2013. Vol. 7, № 3. P. 221–225.

We developed a simple technique for the isolation of NADPH oxidase (Nox) in a soluble form from the brain-cell membrane (BCM) of rats based on the ability of Nox to form an unstable complex with ferrihemoglobin (ferriHb). It was shown for the first time that ferriHb (2 x 10(-6) M) stimulates Nox release from the BCM to the soluble phase after a 2 h aerobic incubation of an aqueous mixture of these membranes at 37A degrees C and pH 8.0 ex vivo. The optical and acid-base characteristics of Nox, as well as the NADPH-dependent O (2) (-) -producing and ferriHb-regenerating activities of the enzyme from the BCM, are similar to the properties of Nox from membranes of other cell types (spleen, erythrocytes, and bone marrow). A synthetic analogue of the neuroactive proline-rich polypeptide (PRP-1) of the neurosecretory granules of the hypothalamus, so-called galarmin (to 10 mg), suppressed ferriHb-induced release of Nox and stimulated the O (2) (-) -producing and ferriHb-regenerating activities of the enzyme in a concentration-dependent manner. We conclude that the release of soluble Nox from the BCM occurs due to membrane destabilization in the presence of ferriHb and that the suppression of Nox release by galarmin may be caused by its membrane-stabilizing effect. The results also suggest that galarmin is involved in the regulation of oxygen homeostasis in brain tissue.


48. U04533
Singh N. et al. Functional bitter taste receptors are expressed in brain cells // Biochem. Biophys. Res. Commun. 2011. Vol. 406, № 1. P. 146–151.

Humans are capable of sensing five basic tastes which are sweet, sour, salt, umami and bitter. Of these, bitter taste perception provides protection against ingestion of potentially toxic substances. Bitter taste is sensed by bitter taste receptors (T2Rs) that belong to the G-protein coupled receptors (GPCRs) superfamily. Humans have 25 T2Rs that are expressed in the oral cavity, gastrointestinal (Cl) neuroendocrine cells and airway cells. Electrophysiological studies of the brain neurons show that the neurons are able to respond to different tastants. However, the presence of bitter taste receptors in brain cells has not been elucidated. In this report using RT-PCR, and immunohistochemistry analysis we show that T2Rs are expressed in multiple regions of the rat brain. RT-PCR analysis revealed the presence of T2R4. T2R107 and T2R38 transcripts in the brain stem, cerebellum, cortex and nucleus accumbens. The bitter receptor T2R4 was selected for further analysis at the transcript level by quantitative real time PCR and at the protein level by immunohistochemistry. To elucidate if the T2R4 expressed in these cells is functional, assays involving G-protein mediated calcium signaling were carried out. The functional assays showed an increase in intracellular calcium levels after the application of exogenous ligands for T2R4, denatonium benzoate and quinine to these cultured cells, suggesting that endogenous T2R4 expressed in these cells is functional. We discuss our results in terms of the physiological relevance of bitter receptor expression in the brain. (C) 2011 Elsevier Inc. All rights reserved.


49. U62187
Stepanichev M.Y. et al. The effects of derivatives of pantothenic acid on free-radical processes and the corticosterone level in the hippocampus and neocortex of rats after interoceptive stress // Neurochem. J. 2013. Vol. 7, № 2. P. 144–149.

In this study, the effects of interoceptive stress on the indices of free-radical oxidation and the corticosterone contents in the brain and blood of male rats were examined. In addition, we studied the effects of the GABA-like nootropic drug calcium hopanthenate and panthenol on these indices after stress. Interoceptive stress was induced by intraperitoneal injection of bacterial lipopolysaccharide and the studies were performed 24 h after injection. The derivatives of pantothenic acid substantially attenuated corticosterone accumulation in the hippocampus after interoceptive stress induced by systemic immune challenge but did not prevent a stress-induced increase in the level of substances that reacted with thiobarbituric acid in the blood of the animals.


50. U04533
Teranishi Y. et al. Erlin-2 is associated with active gamma-secretase in brain and affects amyloid beta-peptide production // Biochem. Biophys. Res. Commun. 2012. Vol. 424, № 3. P. 476–481.

The transmembrane protease complex gamma-secretase is responsible for the generation of the neurotoxic amyloid beta-peptide (A beta) from its precursor (APP). All has a causative role in Alzheimer disease, and thus, gamma-secretase is a therapeutic target. However, since there are more than 70 gamma-secretase substrates besides APP, selective inhibition of APP processing is required. Recent data indicates the existence of several gamma-secretase associated proteins (GSAPs) that affect the selection and processing of substrates. Here, we use a gamma-secretase inhibitor for affinity purification of gamma-secretase and associated proteins from microsomes and detergent resistant membranes (DRMs) prepared from rat or human brain. By tandem mass spectrometry we identified a novel brain GSAP; erlin-2. This protein was recently reported to reside in DRMs in the ER. A proximity ligation assay, as well as co-immunoprecipitation, confirmed the association of erlin-2 with gamma-secretase. We found that a higher proportion of erlin-2 was associated with gamma-secretase in DRMs than in soluble membranes. siRNA experiments indicated that reduced levels of erlin-2 resulted in a decreased A beta production, whereas the effect on Notch processing was limited. In summary, we have found a novel brain GSAP, erlin-2, that resides in DRMs and affects All production. (C) 2012 Elsevier Inc. All rights reserved.


51. U62187
Ukolova T.N., Alekhina T.A., Meshkov I.O. Postural-motor reactions and the distribution of brain monoamines in rats of a catatonic strain at early developmental stages // Neurochem. J. 2012. Vol. 6, № 2. P. 110–115.

Motor responses were studied in neonatal rats of the GC strain, which is characterized by hereditary catatonia. These pups differed from control Wistar pups in having a greater proportion of dyskinetic movements and postures on days 1-2 of neonatal development and a lower number of motor actions in later development. GC pups had elevated noradrenaline levels in the hemispheres on the 7th, 10th, and 14th days in comparison to Wistar rats and in the brainstem on day 10. In GC pups, the amount of serotonin in the hemispheres on days 1 and 14 and in the brainstem on day 14 was lower than in Wistar rats. The level of 5-hydroxyindoleacetic acid in GC pups was lower than in Wistar on days 1 and 7. We compared the characteristics of transmitter mechanisms on the basis of various models: GC rats, pharmacological in vivo models, and spinal in vitro preparations from animals at early developmental stages.


52. U4536X
Urbanczyk A., Juenemann A., Enz R. PKC zeta-interacting protein ZIP3 is generated by intronic polyadenylation, and is expressed in the brain and retina of the rat // Biochem. J. 2011. Vol. 433. P. 43–50.

Scaffold proteins contain multiple protein protein interaction modules that physically assemble functionally related proteins into larger complexes. ZIPs [PKC (protein kinase C) zeta-interacting proteins] link the enzymatic activity of the atypical PKC isoforms PKC lambda/iota or PKC zeta to target proteins and are associated with neurodegenerative disorders. In the rat, alternative splicing generates three ZIP variants. Previously, we identified the ZIP3 transcript, containing 13 C-terminal amino acids encoded by intron 4, in the rat CNS (central nervous system). In the present study, we identified intronic polyadenylation signals in rat and human ZIP genes [known as SQSTM1 (sequestosome-1) in humans] and detected the corresponding ZIP3-like transcripts. In addition, we generated ZIP3-specific immune sera and observed expression of the protein in the brain and retina of the adult rat. In the retina, ZIP3 is present in nuclear layers where it co-localizes with PKC zeta. An immune serum recognizing all three ZIP isoforms labelled the same cells as the newly generated ZIP3-specific antibodies and, in addition, stained both synaptic layers of the retina. There, ZIPs are localized in axon terminals of rod bipolar cells that also contain ZIP-interacting PKC zeta and GABA(C) (gamma-aminobutyric acid type C) receptors. In summary, we detected ZIP3-like transcripts in rat- and human-derived samples and describe the expression of ZIP3 in the rat CNS.


53. U62187
Vasileva E.V., Zolotarev Y.A., Kovalev G.I. The effects of nootropic drugs on metabotropic glutamate receptors in the brains of BALB/c and C57BL/6 mice // Neurochem. J. 2013. Vol. 7, № 2. P. 128–134.

We studied the effects of subchronic administration of various nootropic drugs, such as piracetam, phenotropil, noopept, semax, pantogam, and nooglutil on the neurochemical characteristics of metabotropic glutamate mGluRII receptors in the brains of inbred BALB/c and C57BL/6 mice, which differed in their initial indices of exploratory behavior, anxiety, and locomotor activity. We found that in the brain of the C57BL/6 mice, the B (max) value was 15-20% higher compared to the BALB/c mice. Five daily equipotential doses of the drugs did not influence the B (max) value in all groups of the BALB/c mice, whereas administration of piracetam, noopept, and semax to C57BL/6 mice decreased the density of binding sites for [H-3]-LY354740 by 21, 19, and 18%, respectively. Pantogam and nooglutil did not affect mGluRII binding, suggesting that these drugs have specific mechanism of nootropic action.


54. U62187
Voronkov D.N., Dovedova E.L., Khudoerkov R.M. Interactions between neurotransmitter systems in nigrostriatal structures of rat brain after long-term administration of reserpine and haloperidol // Neurochem. J. 2012. Vol. 6, № 2. P. 116–120.

Using spectrophotometrical methods, we studied the activities of enzymes of dopamine turnover, such as tyrosine hydroxylase and monoamine oxidase B; acetylcholine turnover, such as acetylcholinesterase; and glutamate metabolism, such as glutamine synthetase in the caudate nucleus and substantia nigra of the brain of Wistar rats after a 14 day administration of reserpine and haloperidol. We found inhibition of synthesis and catabolism of dopamine and activation of the cholinergic system due to the inhibition of acetylcholine esterase. We found specific changes in the cholinergic and glutamatergic systems associated with disturbances in dopaminergic turnover after application of reserpine and haloperidol.


55. Wang X.-J. et al. Dibutyl Phthalate Inhibits the Effects of Follicle-Stimulating Hormone on Rat Granulosa Cells Through Down-Regulation of Follicle-Stimulating Hormone Receptor // Biol. Reprod. 2016. Vol. 94, № 6. P. 144.

Dibutyl phthalate (DBP) is used worldwide in solvents and plasticizers. The cytotoxicity and potential tumorigenic effect of DBP have been reported. DBP has also been shown to impact reproductive function. In this study, to further evaluate the effects of DBP on granulosa cells (GCs), we treated rat GCs in vitro with DBP before evaluation of the biological alterations of these GCs. We found that DBP did not induce significant GC death at the tested concentrations. However, follicle-stimulating hormone (FSH)-induced KIT ligand (KITLG) expression in GCs was significantly reduced at both mRNA and protein levels by DBP treatment in a dose-dependent manner. The down-regulation of KITLG was due to the down-regulation of expression of FSH receptor (FSHR) in GCs. Down-regulation of FSHR impaired FSH-induced intracellular signaling in GCs, demonstrated by decreased phosphorylation of AKT and mechanistic target of rapamycin (mTOR). Furthermore, DBP treatment also reduced FSH-induced expression of hypoxia-inducible factor 1-alpha (HIF1A), which is an important signaling component for KITLG expression. Other FSH-induced biological effects, such as production of estradiol and progesterone, as well as GC proliferation, were also suppressed by DBP. Therefore, our study discovered a unique mechanism underlying the toxicity of DBP on GCs. These findings may initiate the development of novel therapeutic interventions for DBP-induced damage to GCs.


56. U07870
Watson E. et al. Interspecies Systems Biology Uncovers Metabolites Affecting C. elegans Gene Expression and Life History Traits // Cell. 2014. Vol. 156, № 4. P. 759–770.

Diet greatly influences gene expression and physiology. In mammals, elucidating the effects and mechanisms of individual nutrients is challenging due to the complexity of both the animal and its diet. Here, we used an interspecies systems biology approach with Caenorhabditis elegans and two of its bacterial diets, Escherichia coli and Comamonas aquatica, to identify metabolites that affect the animal's gene expression and physiology. We identify vitamin B12 as the major dilutable metabolite provided by Comamonas aq. that regulates gene expression, accelerates development, and reduces fertility but does not affect lifespan. We find that vitamin B12 has a dual role in the animal: it affects development and fertility via the methionine/S-Adenosylmethionine (SAM) cycle and breaks down the short-chain fatty acid propionic acid, preventing its toxic buildup. Our interspecies systems biology approach provides a paradigm for understanding complex interactions between diet and physiology.


57. 00651400
Xu X. et al. Aberrant changes of somatostatin and neuropeptide Y in brain of a genetic rat model for epilepsy: tremor rat // Acta Neurobiol. Exp. 2016. Vol. 76, № 3. P. 165–175.

Excessive excitation or loss of inhibitory neurotransmission has been closely related to epileptic activity. Somatostatin (SST) and Neuropeptide Y (NPY) are members of endogenous neuropeptides which are recognized as important modulator of classical neurotransmitter, distributed abundantly in mammalian central nervous system. Abnormal expression of these two neuropeptides evidenced in some epileptic models highlights the relevance of SST or NPY in the pathogenesis of epilepsy. The tremor rat (TRM) is a genetic epileptic animal model which can manifest tonic convulsions without any external stimuli. The present study aimed to investigate the distribution and expression of SST and NPY in TRM brains, including hippocampus, temporal lobe cortex and cerebellum. Our RT-PCR data showed that up-regulated mRNA expression of SST and NPY was discovered in TRM hippocampus and temporal lobe cortex compared with control (Wistar) rats. The peptide levels of these neuropeptides in brain areas mentioned above were both apparently higher than that in normal Wistar rats as well. However, in cerebellums, neither SST nor NPY was significantly changed compared with control group. The immunohistochemical data showed that SST and NPY were widely present throughout CA1, CA3 and the hilus of hippocampus, the entorhinal cortex of temporal lobe cortex, as well as cerebellar Purkinje layer. In conclusion, our results discovered the aberrant changes of SST and NPY in several TRM brain regions, suggesting that the peptidergic system might be involved in TRM epileptiform activity.

58. Yin F.J. et al. Effect of dehydroepiandrosterone treatment on hormone levels and antioxidant parameters in aged rats // Genet. Mol. Res. 2015. Vol. 14, № 3. P. 11300–11311.

The aim of the current study was to evaluate the effect of chronic dehydroepiandrosterone (DHEA) administration on steroid hormones and antioxidant parameters in aged rats. To this end, three groups of Sprague-Dawley rats were compared: young (3 months of age) untreated; aged (19 months old) untreated; and aged rats treated with 20 mg/kg DHEA for 8 weeks. Major organs of aged rats in the untreated group demonstrated physiological atrophy, compared to those of young rats; this effect appeared to have been partially reversed by DHEA treatment. Testosterone and estradiol contents were significantly decreased and aldosterone significantly increased in aged untreated, compared to young untreated rats. Steroid hormone levels were obviously reversed, however, in aged rats treated with DHEA. Additionally, superoxide dismutase activity in serum, brain, heart, and liver was decreased, and maleic dialdehyde content in heart was markedly increased in untreated aged, compared to young, rats. Importantly, these changes in brain and heart of aged rats were reversed by DHEA treatment. Heme oxygenase mRNA levels were increased and inducible nitric oxide synthase mRNA levels decreased in aged, compared to young, rats; DHEA treatment appeared to reverse these changes. These results indicate that chronic DHEA administration may have effects on steroid hormone levels and antioxidant parameters in aged rats and result in postponement of the aging process.


59. U07902
Zhang J. et al. Allogeneic adipose-derived stem cells promote survival of fat grafts in immunocompetent diabetic rats // Cell and Tissue Research. 2016. Vol. 364, № 2. P. 357–367.

Autologous adipose-derived stem cells (ADSCs) can protect fat grafts in cell-assisted lipotransfer (CAL). However, diabetes alters the intrinsic properties of ADSCs and impairs their function so that they lack these protective effects. We investigate whether allogeneic ADSCs from healthy donors could protect fat grafts in immunocompetent diabetic rats. Syngeniec adipose tissues and ADSCs were derived from diabetic Lewis (LEW) rats, whereas allogeneic ADSCs were from healthy brown-Norway rats. A grafted mixture containing 0.7 ml granule fat and 0.3 ml 6 x 10(6) allogeneic/syngeneic ADSCs was injected subcutaneously on the skulls of diabetic LEW rats. Fat samples were harvested to evaluate the levels of injury and vascularization as shown by perilipin A, CD34 and VEGF at 14 days. The immune response was evaluated with a lymphocytotoxicity test and the CD4/CD8 ratio in peripheral blood at 14 days. The volume retention of fat grafts was measured at 3 months. Healthy allogeneic ADSCs increased the expression levels of perilipin A, CD34 and VEGF at 14 days. The volume retention of fat grafts was improved by allogeneic ADSCs at 3 months. ADSCs were demonstrated to have low immunogenicity by the lymphocyte proliferation test and immunophenotype including MHC and co-stimulatory markers. The lymphocytotoxicity test and CD4/CD8 ratio indicated no obvious immune response elicited by allogeneic ADSCs. Thus, healthy allogeneic ADSCs can promote the survival of fat grafts in this immunocompetent diabetic rat model, with little or no obvious immune rejection.


60. U04533
Zhang S. et al. AT motif binding factor 1 (ATBF1) is highly phosphorylated in embryonic brain and protected from cleavage by calpain-1 // Biochem. Biophys. Res. Commun. 2012. Vol. 427, № 3. P. 537–541.

ATBF1 is a transcription factor that regulates genes responsible for repairing tissues and the protection of cells from oxidative stress. Therefore reduction of ATBF1 promotes susceptibility to varieties of human diseases including neurodegenerative diseases and malignant tumors. The instability of the protein was found to be an important background of diseases. Because ATBF1 is composed of a large 404-kDa protein, it can be easily targeted by proteinases. The protein instability should be a serious problem for the function in the cells and practically for our biochemical study of ATBF1. We have found that calpain-1 is a protease responsible for the degeneration of ATBF1. We observed distinct difference between embryo and adult brain derived ATBF1 regarding the sensitivity to calpain-1. The comparative study showed that eight phosphorylated serine residues (Ser1600, Ser2634, Ser2795, Ser2804, Ser2900, Ser3431, Ser3613, Ser3697) in embryonic brain, but only one site (Ser2634) in adult brain. As long as these amino acids were phosphorylated, ATBF1 derived from embryonic mouse brain showed resistance to cleavage: however, treatment with calf intestine alkaline phosphatase sensitized ATBF1 to be digested by calpain-1. An inhibitor (FK506) against calcineurin, which is a serine/threonine specific phosphatase enhanced the resistance of ATBF1 against the digestion by calpain-1. Taken together, these results demonstrate that these phosphorylation sites on ATBF1 function as a defensive shield to calpain-1. (C) 2012 Elsevier Inc. All rights reserved.


61. U04533
Zhu C. et al. Repeated exposure of the developing rat brain to magnetic resonance imaging did not affect neurogenesis, cell death or memory function // Biochem. Biophys. Res. Commun. 2011. Vol. 404, № 1. P. 291–296.

The effect of magnetic fields on the brain is a matter of debate. The objective of this study was to investigate whether repeated exposure to strong magnetic fields, such as during magnetic resonance imaging (MRI), could elicit changes in the developing rat brain. Embryonic day 15 (E15) and postnatal day 14 (P14) rats were exposed to MRI using a 7.05 T MR system. The animals were anesthetized and exposed for 35 min per day for 4 successive days. Control animals were anesthetized but no MRI was performed. Body temperature was maintained at 37 degrees C. BrdU was injected after each session (50 mg/kg). One month later, cell proliferation, neurogenesis and astrogenesis in the dentate gyrus were evaluated, revealing no effects of MRI, neither in the EIS, nor in the P14 group. DNA damage in the dentate gyrus in the P14 group was evaluated on P18, 1 day after the last session, using TUNEL staining. There was no difference in the number of TUNEL-positive cells after MRI compared with controls, neither in mature neurons, nor in newborn progenitors (BrdU/TUNEL double-labeled cells). Novel object recognition was performed to assess memory function 1 month after MRI. There was no difference in the recognition index observed after MRI compared with the control rats, neither for the E15, nor for the P14 group. In conclusion, repeated exposure to MRI did not appear to affect neurogenesis, cell death or memory function in rats, neither in late gestation (E15-E18) nor in young postnatal (P14-P17) rats. (C) 2010 Elsevier Inc. All rights reserved.


62. 010021
Авалиани Т.В., Константинов К.В., Сизов В.В., Цикунов С.Г. ОСОБЕННОСТИ ПРОСТРАНСТВЕННО-ВРЕМЕННOЙ ОРГАНИЗАЦИИ БИОЭЛЕКТРИЧЕСКОЙ АКТИВНОСТИ МОЗГА У ПОТОМСТВА ОТ КРЫС С ЛАТЕРАЛИЗОВАННОЙ ТРАВМОЙ МОЗГА // Российский физиологический журнал им. И.М. Сеченова. 2013. Т. 99. № 10. С. 1149-1159.

Исследованы особенности пространственно-временнoй организации биоэлектрической активности мозга у потомства от крыс с латерализованной травмой сенсомоторной коры мозга. Кросскореляционный анализ электрокортикограммы (ЭКоГ) выявил у одномесячных животных достоверное изменение фазовых соотношений биоэлектрических процессов в различных точках регистрации. Изменение межструктурных связей по ЭКоГ-показателям у крысят коррелировало с выраженностью нарушений поведения в тесте «открытое поле» (ОП). Наиболее значимые изменения пространственно-временнoй организации биоэлектрической активности (уменьшение синхронной активности между лобными отведениями) регистрировались у крысят с выраженным нарушением поведения по сравнению с животными тех же групп, у которых поведение незначительно отличалось от нормы. Нарушение целостности поведения в тесте ОП сопровождалось уменьшением синхронной активности между левой лобной и правой затылочной областью или уменьшением показателей опережающей активности в правой лобной области по отношению к правой затылочной области. При сохранении целостности поведения эти показатели были увеличены по сравнению с контролем.


63. 000513
Акопова О.В., Колчинская Л.И., Носарь В.И., Бурый В.А., Маньковская И.Н., Сагач В.Ф. ВЛИЯНИЕ ПОТЕНЦИАЛЗАВИСИМОГО ВХОДА КАЛИЯ НА АККУМУЛЯЦИЮ КАЛЬЦИЯ В МИТОХОНДРИЯХ МОЗГА КРЫС // Биохимия. 2013. Т. 78. № 1. С. 106-117.

Изучено влияние потенциалзависимого входа калия на накопление кальция в митохондриях мозга крыс. В области концентраций К+ 0-120 мМ потенциалзависимый вход К+ приводит к повышению скорости дыха- ния и внутримитохондриального рН за счет выхода протонов из матрикса митохондрий. Показано, что на- копление Са2+ зависит от концентрации К+ в среде. При концентрациях К+ 30 мМ накопление Са2+ сни- жается, по сравнению с контролем, вследствие К+-индуцированной деполяризации митохондрий, тогда как с повышением концентрации К+ вход Са2+ в матрикс, напротив, повышается, несмотря на деполяризацию мембраны, вследствие обусловленного входом К+ повышения внутримитохондриального рН. Селективные блокаторы митохондриального АТР-зависимого К+-канала (K+ ATP-канала), глибенкламид и 5-гидроксидека- ноат, ослабляют эффекты потенциалзависимого транспорта К+. Это приводит к повышению аккумуляции Са2+ вследствие уменьшения деполяризующего эффекта калия при его низких концентрациях, но в то же время, к снижению накопления Са2+ при высоких концентрациях калия в среде вследствие уменьшения за- щелачивания матрикса при накоплении ионов К+ митохондриями. Результаты экспериментов показывают, что потенциалзависимый транспорт К+, в том числе и АТР-зависимый, является важным регулятором на- копления кальция в митохондриях.


64. 000617
Алексеева Е.В., Назарова Г.А., Судаков С.К. ВЛИЯНИЕ АГОНИСТОВ ПЕРИФЕРИЧЕСКИХ M-, D- И K-ОПИОИДНЫХ РЕЦЕПТОРОВ НА УРОВЕНЬ ТРЕВОЖНОСТИ И ДВИГАТЕЛЬНОЙ АКТИВНОСТИ КРЫС // Бюллетень экспериментальной биологии и медицины. 2012. Т. 153. № 5. С. 677-679.

Изучали влияние интрагастрального введения пептидных агонистов m-опиоидных рецепторов DAMGO, d-опиоидных рецепторов DADLE и k-опиоидных рецепторов ICI 204,448 на показатели тревожности и двигательной активности крыс в крестообразном приподнятом лабиринте. Показано, что периферическое введение ICI 204,448 оказывает анксиолитическое действие и не влияет на двигательную активность крыс. Введение DAMGO и DADLE снижает двигательную активность крыс, при этом DADLE также повышает уровень тревожности. Полученные данные о разнонаправленном воздействии ICI 204,448 и DADLE на уровень тревожности крыс подтверждают выдвинутую нами ранее гипотезу о взаимодействии центрального и периферического звеньев эндогенной опиоидной системы.


65. 010021
Амахин Д.В., Попов В.А., Малкиель А.И., Веселкин Н.П. ОСОБЕННОСТИ СУММАЦИИ ГАМК- И ГЛУТАМАТ-ОПОСРЕДОВАННЫХ ИОННЫХ ТОКОВ ИЗОЛИРОВАННЫХ НЕЙРОНОВ КОРЫ ГОЛОВНОГО МОЗГА КРЫСЫ // Российский физиологический журнал им. И.М. Сеченова. 2012. Т. 98. № 12. С. 1490-1506.

В изолированных нейронах префронтальной коры головного мозга крыс методом пэтч-кламп в конфигурации «целая клетка» проведено исследование особенностей суммации ионных токов, вызванных аппликациями глутамата и ГАМК. Для регистрации ионных токов использовалось два различных пипеточных раствора: на основе хлорида и фторида цезия. При регистрации с применением раствора на основе хлорида цезия пиковая амплитуда тока, вызванного совместной аппликацией ГАМК и глутамата (по 200 мкМ), совпадала с пиковой амплитудой тока, вызванного аппликацией только ГАМК, и была достоверно меньше арифметической суммы амплитуд ответов на аппликации нейромедиаторов по отдельности. При использовании пипеточного раствора на основе фторида цезия ответ на совместную аппликацию смеси глутамата и ГАМК практически совпадал с арифметической суммой индивидуальных ответов. При действии этих нейромедиаторов в насыщающих концентрациях (5 мМ) регистрируемый ответ на совместную аппликацию был достоверно меньше, чем ответ на аппликацию только ГАМК. Полученные результаты позволяют предположить наличие механизма взаимодействия между ГАМК А- и ионотропными глутаматными рецепторами (АМРА и каинатными). По-видимому, при совместной аппликации глутамата и ГАМК активация ГАМК А-рецепторов в большей мере влияет на глутаматные рецепторы, чем активация глутаматных на ГАМК А-рецепторы.


66. 010021
Борзых А.А., Гайнуллина Д.К., Кузьмин И.В., Шарова А.П., Тарасова О.С., Виноградова О.Л. СРАВНИТЕЛЬНЫЙ АНАЛИЗ ЭКСПРЕССИИ ГЕНОВ В ЛОКОМОТОРНЫХ МЫШЦАХ И ДИАФРАГМЕ КРЫСЫ // Российский физиологический журнал им. И.М. Сеченова. 2012. Т. 98. № 12. С. 1587-1594.

Методом количественной ПЦР исследовали профиль экспрессии генов в диафрагме по сравнению с тремя принципиально различными по характеристикам мышцами задней конечности (камбаловидной мышцей, красной и белой частями икроножной мышцы). Показано, что уровни экспрессии мРНК PGC-1? и миогенина в диафрагме находятся в соответствии с ее миозиновым фенотипом и активностью цитратсинтазы. Вместе с тем диафрагма характеризуется необычно высоким содержанием мРНК MyoD, а также высоким содержанием мРНК IGF-1 и низким содержанием мРНК миостатина. Последние два наблюдения позволяют предположить высокую интенсивность белкового синтеза в мышечных волокнах диафрагмы, несмотря на то что они мельче, чем в локомоторных мышцах.


67. 010322

Спектрофотометрически исследовали удельную активность ферментов обмена дофамина (тирозингидроксилаза, моноаминоксидаза Б), ацетилхолина (ацетихолинэстераза), глутамата (глутаминсинтетаза) в хвостатом ядре и черной субстанции мозга крыс Вистар под влиянием длительного, в течение 14 дней, воздействия препаратов резерпина и галоперидола. Показано подавление синтеза и катаболизма дофамина и активация холинергической системы при подавлении активности ацетилхолинэстеразы. Отмечены особенности изменений холинергической и глутаматергической систем, связанные с нарушением дофаминергического обмена под действием резерпина и галоперидола.


68. 000231
Григорьев И.П., Шкляева М.А., Кирик О.В., Гилерович Е.Г., Коржевский Д.Э. РАСПРЕДЕЛЕНИЕ АЛЬФА-ТУБУЛИНА В СТРУКТУРАХ ПЕРЕДНЕГО МОЗГА КРЫСЫ // Морфология. 2013. Т. 143. № 1. С. 007-010.

Иммуногистохимически исследовано распределение белка микротрубочек ?-тубулина в структурах переднего мозга крысы. Обнаружена неравномерность окраски при реакции на ?-тубулин. Высокая иммунореактивность выявлена в поясной и пириформной коре, обонятельных бугорках и перекресте зрительных нервов. Наиболее слабая иммуногистохимическая реакция отмечена в полосатом теле, поверхностных слоях перегородки, поясе и структурах вокруг III желудочка мозга. Иммунореактивность в нейронах была отчетливо выражена по периферии перикариона и в апикальном дендрите. Высказано предположение, что интенсивность иммуногистохимической реакции на ?-тубулин может отражать уровень функционального состояния нейронов.


69. 010021
Диатроптов М.Е., Кондашевская М.В., Макарова О.В., Обернихин С.С. ИНФРАДИАННЫЕ РИТМЫ МОРФОФУНКЦИОНАЛЫЮГО СОСТОЯНИЯ ТИМУСА У КРЫС // Российский физиологический журнал им. И.М. Сеченова. 2013. Т. 99. № 6. С. 729-736.

В работе представлены результаты длительных исследований биоритмов клеточного состава тимуса, мелатонина и кортикостерона половозрелых самцов крыс линии Вистар. Показатели общего числа клеток в тимусе, числа лимфоцитов в периферической крови и процентного содержания CD3 + лимфоцитов имели период колебаний, равный 6 суткам. Биоритмы с другим периодом — 4 суток — обнаружены в динамике показателей ширины субкапсулярного слоя коры тимуса и включения тимидиновой метки. Биоритмы уровня мелатонина и кортикостерона имеют период 4 суток и находятся в противофазе.


70. 000231

Целью исследования явилась оценка структурных и метаболических изменений в клетках Пуркинье (КП) мозжечка крыс в динамике подпеченочного холестаза. Использованы гистологические, гистохимические и электронно-микроскопические методы. Установлено, что холестаз вызывает прогрессивное нарастание структурных и метаболических нарушений в КП мозжечка с максимумом на 10–20-е сутки, приводящих к гибели и уменьшению их числа. В цитоплазме этих нейронов происходит снижение активности дегидрогеназ: сукцината, NADH, глюкозо-6-фосфата и уменьшение содержания РНК, но активация лактатдегидрогеназы и кислой фосфатазы. Нарушения ультраструктуры клеток Пуркинье включали деструкцию ядра и органелл (особенно митохондрий), что сопровождалось увеличением количества и размеров лизосом и фагосом, увеличением относительного числа свободных рибосом, появлением тесных контактов митохондрий с ядром и органеллами. Через 45–90 сут у выживших животных происходила постепенная нормализация структуры и метаболизма КП мозжечка вследствие самопроизвольного устранения холестаза, по-видимому, в результате образования обходных желчевыводящих путей.


71. 000617
Калиниченко Л.С., Перцов С.С., Коплик Е.В., Пирогова Г.В. АНТИОКСИДАНТНАЯ ЗАЩИТА ГОЛОВНОГО МОЗГА КРЫС ПРИ ОСТРОЙ СТРЕССОРНОЙ НАГРУЗКЕ И ВВЕДЕНИИ ИНТЕРЛЕЙКИНА-1B // Бюллетень экспериментальной биологии и медицины. 2012. Т. 153. № 5. С. 635-638.

Изучали влияние ИЛ-1b на активность антиоксидатных ферментов в эмоциогенных структурах головного мозга (гипоталамусе, сенсомоторной коре, миндалине) у поведенчески пассивных и активных крыс с разной устойчивостью к стрессу. В качестве модели стрессорной нагрузки использовали часовую иммобилизацию животных с одновременным электрокожным раздражением. Внутрибрюшинное введение ИЛ-1b (5 мкг/кг) приводило к снижению активности глутатионредуктазы в гипоталамусе крыс. У активных животных, получавших ИЛ-1b, отмечено увеличение активности Cu/Zn-супероксиддисмутазы в сенсомоторной коре и глутатионпероксидазы в миндалине. Введение ИЛ-1b сопровождалось активацией Cu/Zn-супероксиддисмутазы и глутатионпероксидазы в миндалине пассивных крыс. Предварительное введение ИЛ-1b предупреждало постстрессорные изменения активности ферментов в гипоталамусе активных особей и сенсомоторной коре пассивных крыс. Полученные результаты отражают особенности воздействия ИЛ-1b на антиоксидантную защиту тканей ЦНС у крыс с разными типами поведения.


72. 000231
Кирик О.В., Алексеева О.С., Коржевский Д.Э. ЭКСПРЕССИЯ МАРКЕРА НЕЙРАЛЬНЫХ СТВОЛОВЫХ КЛЕТОК MSI-1 В КОНЕЧНОМ МОЗГУ КРЫСЫ // Морфология. 2011. Т. 139. № 2. С. 77-79.

Цель исследования состояла в изучении распределения клеток, экспрессирующих белок Musashi-1 (Msi-1), считающийся маркером нейральных стволовых клеток, в конечном мозгу крысы. Установлено, что такие клетки концентрируются в субвентрикулярной пролиферативной зоне и диффузно распределены в стриатуме и гиппокампе. Кроме того, интенсивную реакцию на Msi-1 дают нейроны ядра поводка. Полученные результаты не вполне согласуются с существующими представлениями о местах локализации нейральных стволовых клеток в головном мозгу.


73. 000231
Кирик О.В., Коржевский Д.Э.ВНЕЭПЕНДИМНЫЕ ЭПЕНДИМОЦИТЫ ГОЛОВНОГО МОЗГА КРЫСЫ // Морфология. 2013. Т. 143. № 3. С. 071-073

Цель работы состояла в проверке гипотезы о существовании в интактном головном мозгу крысы клеток, которые по структурной организации и цитохимическим характеристикам сходны с эпендимоцитами, но расположены вне слоя эпендимы. Работа выполнена на крысах линии Вистар (n=10). Для идентификации эпендимоцитов использовали иммуноцитохимические реакции на эзрин и виментин, световую и конфокальную лазерную микроскопию. Установлено, что в нервной ткани интактного головного мозга крысы вне слоя эпендимоцитов присутствуют клетки, имеющие структурное и цитохимическое сходство с типичными клетками эпендимы. Предполагается, что внеэпендимные эпендимоциты выполняют функцию резервной популяции нейральных стволовых клеток головного мозга.


74. 000231

Целью исследования было выявление колонок неокортекса поля S1 на фронтальных срезах головного мозга у белых беспородных крыс (n=10) с использованием метода иммуногистохимии и антител к белкам нейронов (синаптофизину, нейрофиламентам) и глиоцитов (глиальному фибриллярному кислому белку - GFAP, основному белку миелина). Изучение экспрессии основных нейроспецифических антигенов позволило установить, что на тонких срезах (4 мкм) колонку можно идентифицировать благодаря скоплениям астроцитов и отростков нейронов - аксонов и дендритов. Исследование экспрессии GFAP также показало, что в I слое коры, как правило, содержатся большое количество крупных астроцитов с ветвящимися отростками, а также многочисленные мелкие отростки с высокой интенсивностью экспрессии. Содержание синаптофизина - высокое во всех слоях коры, но наиболее интенсивная реакция выявлена в молекулярном слое, так же как и при реакции на GFAP. Экспрессия основного белка миелина выявляется, соответственно, радиально расположенным миелинизированным отросткам нейронов в коре.


75. 000617
Козлов А.Ю., Абрамова А.Ю., Никенина Е.В. НОЦИЦЕПТИВНЫЕ ПОРОГИ У КРЫС ПРИ ВВЕДЕНИИ ЛПС В СПЕЦИФИЧЕСКИЕ ЯДРА ТАЛАМУСА ГОЛОВНОГО МОЗГА // Бюллетень экспериментальной биологии и медицины. 2012. Т. 154. № 12. С. 674-676.

Микроинъекции ЛПС в специфические ядра таламуса головного мозга крыс (вентробазальный комплекс ядер -- VPL и VPM) приводят к незначительному усилению перцептуального и достоверному снижению эмоционального компонентов системной болевой реакции.


76. 000617
Козлов А.Ю., Абрамова А.Ю., Никенина Е.В., Мезенцева Л.В. НОЦИЦЕПТИВНЫЕ ПОРОГИ У КРЫС ПРИ ВВЕДЕНИИ ЛИПОПОЛИСАХАРИДА В ЛИМБИЧЕСКИЕ СТРУКТУРЫ ГОЛОВНОГО МОЗГА // Бюллетень экспериментальной биологии и медицины. 2012. Т. 153. № 5. С. 689-692.

Показано, что микроинъекции ЛПС в лимбические структуры головного мозга крыс (дорсальный гиппокамп и каудальный отдел поясного пучка) приводят к разнонаправленному воздействию на ноцицептивные пороги: введение препарата в дорсальный гиппокамп вызывает усиление перцепции и снижение эмоционально-аффективного восприятия боли, в поясной пучок -- снижает перцептуальный и усиливает эмоциональный компоненты ноцицептивной реакции. Полученные результаты свидетельствуют о специфическом участии указанных лимбических структур в модуляции ноцицепции при индукции иммунного ответа в ЦНС.


77. 000617
Колобов В.В., Сторожева З.И., Грудень М.А., Шерстнев В.В. РЕГИОНАЛЬНЫЕ ОСОБЕННОСТИ ЭКСПРЕССИИ ГЕНОВ НЕЙРОГЕНЕЗА И АПОПТОЗА В ГОЛОВНОМ МОЗГЕ ЗРЕЛЫХ КРЫС // Бюллетень экспериментальной биологии и медицины. 2012. Т. 153. № 5. С. 707-711.

В префронтальной коре, гиппокампе и мозжечке взрослых крыс определяли экспрессию мРНК генов, вовлеченных в нейрогенез и апоптоз: Apaf1, Ascl1, Bax, Bcl2, Casp3, Casp8, Casp9, Dffb, Myh10, Naip2, Napa, Notch2, Numb, Pura, S100a6 и Tnf. Обнаружено, что в мозжечке относительное содержание мРНК указанных генов, за исключением Apaf1, многократно увеличено по сравнению с их уровнем в гиппокампе и коре мозга, тогда как в гиппокампе по сравнению с префронтальной корой значимо снижена экспрессия Apaf1 и увеличена экспрессия Ascl1, Pura, S100a6 и Tnf. Выявлены региональные различия в направленности, силе и количестве достоверных корреляций между относительными уровнями экспрессии исследованных генов. Документированные особенности генной экспрессии рассматриваются как подтверждение положения о структурно-функциональной сопряженности процессов нейрогенеза и нейроапоптоза на молекулярно-генетическом уровне.


78. 000231

Известно, что при развитии головного мозга по мере дифференцировки эпендимоцитов из радиальных глиоцитов происходит прекращение синтеза нестина. Однако показано, что нестин в эпендиме боковых желудочков головного мозга начинает синтезироваться в ответ на ишемическое повреждение. Цель настоящего исследования состояла в проверке гипотезы о возможности восстановления экспрессии нестина в эпендиме при старении. Работа выполнена на крысах-самцах линии Вистар в возрасте 4 (n=4) и 28 мес (n=3). У старых животных установлена экспрессия нестина в эпендиме боковых желудочков головного мозга, причем в области медиальной и верхней стенок бокового желудочка обнаружены участки эпендимы, в которых все клетки имели интенсивную окраску цитоплазмы. Причины обнаруженного факта остаются неясными.


79. 000231

Одной из мало исследованных проблем патогенеза ишемического повреждения головного мозга является ранняя реорганизация кровеносных сосудов в зоне транзиторной ишемии. Цель настоящего исследования состояла в изучении структурной организации и цитохимических характеристик гладких миоцитов (ГМ) стенки внутримозговых кровеносных сосудов у 16 крыс Вистар в ранний постишемический период (через 48 ч после 30-минутной ишемии). При изучении поврежденного полушария обнаружены звездчатые клетки, дающие реакцию на ?-гладкомышечный актин, представляющие собой, по-видимому, особую популяцию структурно измененных ГМ, не характерных для интактного мозга контрольных животных (n=5). Функциональная роль этих клеток остается неясной.


80. 00066X
Костин Н.А., Сафарьянц Н.Г. ОСОБЕННОСТИ РАННЕГО ПОСТНАТАЛЬНОГО ОНТОГЕНЕЗА НЕОКОРТЕКСА МОЗГА КРЫСЫ // Вестник Санкт-Петербургского университета. Серия 3. Биология. 2011. № 1. С. 50-56.

Исследованы цитоархитектоника и дифференцировка пирамидных нейронов сенсомоторной коры мозга крысы на ранних этапах постнатального развития. Задачи исследования - изучить особенности раннего постнатального развития сенсомоторной коры мозга с помощью метода Ниссля и морфометрического анализа, и также иммуногистохимически, используя антитела к белкам МАР2 и N200. Гистологический метод окрашивания тел нервных клеток тионином (метод Ниссля) позволил установить постепенное усложнение цитоархитектоники коры мозга крысы в течение первых трех недель жизни. В возрасте 7 дней кортикальная пластинка слабо стратифицирована, однако на 15-й день она начинает расслаиваться, и к 20-му дню кора приобретает строение, характерное для взрослого животного. Метод морфометрического анализа позволил объективно выделить кластеры клеток, соответствующие цитоархитектоническим слоям, и показал усложнение кластеризации в течение первых трех недель постнатального онтогенеза. Иммуногистохимический метод, с применением антител к белку МАР2, дал возможность выявить последовательность дифференцировки нейронов коры мозга крысы в течение первых трех недель жизни. Было обнаружено, что MAP2-позитивные нейроны появляются в V слое коры на 15-й день, а в III - на 20-й день постнатального онтогенеза. Иммуногистохимическое исследование с применением антител к белку N200 позволило определить функциональную специализацию пирамидных нейронов. N200-позитивные нейроны были выявлены только в V слое коры, также была показана колоколизация белков MAP2 и N200 в этих нейронах.


81. 000231
Коцюба А.Е., Черток В.М. РАСПРЕДЕЛЕНИЕ ГЕМОКСИГЕНАЗЫ-2 В ЯДРАХ СТВОЛА ГОЛОВНОГО МОЗГА КРЫСЫ // Морфология. 2012. Т. 142. № 6. С. 015-019.

Иммуноцитохимическим методом изучено распределение нейронов, экспрессирующих гемоксигеназу-2 (ГО-2), в ядрах различных отделов ствола головного мозга 16 крыс-самцов линии Вистар. В различных ядрах определяли размеры нейронов и оптическую плотность продукта гистохимической реакции в их цитоплазме. В ядрах продолговатого мозга, моста и среднего мозга выявлены ГО-2-позитивные нейроны, различающиеся формой, количеством и размерами. Установлено, что в чувствительных ядрах ГО-2-позитивные клетки встречаются в 3–5 раз чаще, чем в двигательных. Между тем, имеется относительно большое количество как чувствительных, так и двигательных ядер, в которых ГО-2-позитивные нейроны не выявляются или определяются лишь в виде единичных клеток.


82. 010021
Кратирова Н.В., Веселкина О.С., Колпакова М.Э., Чефу С.Г., Коржевский Д.Э., Дайнеко А.С., Просвирнина М.С., Пискун А.В., Власов Т.Д. ЭФФЕКТ ВНУТРИГАСТРАЛЫЮГО ВВЕДЕНИЯ КРЕАТИНИЛГЛИЦИН ЭТИЛОВОГО ЭФИРА ФУМАРАТА ПРИ ОККЛЮЗИОННОЙ ИШЕМИИ МОЗГА У КРЫС // Российский физиологический журнал им. И.М. Сеченова. 2012. Т. 98. № 10. С. 1258-1263.

Целью исследования являлась оценка нейропротективного действия креатинилглицин этилового эфира фумарата (препарата креамид). Методика включала внутригастральное введение креамида в дозе 30 и 50 мг/кг 2 раза в сутки в течение 10 дней. Модель фокальной 30-минутной ишемии головного мозга воспроизводилась эндоваскулярно с последующим периодом реперфузии 48 ч. Определяли стабильность креамида в желудочном соке, процентное отношение площади некроза, а также производили гистологическое исследование и выявляли неврологический дефицит у крыс. В результате были получены данные о достоверном нейропротективном эффекте креамида в дозе 50 мг/кг 2 раза в сутки, который уменьшал ишемическое и реперфузионное повреждение головного мозга.


83. 033254
Крючкова А.В., Иноземцев А.Н., Арион В.Я., Лосева Е.В. ДОЗОЗАВИСИМОЕ ВЛИЯНИЕ ТАКТИВИНА НА ПОВЕДЕНИЕ КРЫС И ЧИСЛО ЯДРЫШЕК В НЕЙРОНАХ НЕКОТОРЫХ СТРУКТУР ИХ МОЗГА // Нейрокомпьютеры: разработка, применение. 2014. № 7. С. 24-30.

Рассмотрено влияние двух доз тактивина, вводимых интраназально, на поведение животных в тестах «открытое поле», «темно-светлая камера» и «приподнятый крестообразный лабиринт», и на число ядрышек в нейронах трех структур головного мозга крыс. Было обнаружено, что у животных, получавших малую дозу тактивина, незначительно усиливалась двигательная и исследовательская активность, что может свидетельствовать о снижении уровня тревожности. Животные, получавшие большую дозу препарата, показывали тревожно-депрессивный паттерн поведения. Длительное введение тактивина в обеих дозах уменьшило число ядрышек в пирамидных нейронах поля СА1 гиппокампа и в больших пирамидах V слоя сенсомоторной области неокортекса, но не изменило число ядрышек в нейронах головки хвостатого ядра.


84. 010322
Матвеева М.И., Штемберг А.С., Тимошенко Г.Н., Красавин Е.А., Наркевич В.Б., Клодт П.М., Кудрин В.С., Базян А.С. ВЛИЯНИЕ ОБЛУЧЕНИЯ ИОНАМИ УГЛЕРОДА 12C НА ОБМЕН МОНОАМИНОВ В НЕКОТОРЫХ СТРУКТУРАХ МОЗГА КРЫС // Нейрохимия. 2013. Т. 30. № 4. С. 343.

Крыс облучали ионами углерода (12C) на ускорителе “Нуклотрон”. Доза облучения ? 1 Гр, энергия ионов ? 500 МэВ/нуклон, линейная передача энергии (ЛПЭ) ? 10.6 кэВ/микрон. Животных декапитировали через 1 сут после облучения, выделяли следующие структуры мозга: префронтальная кора, прилежащее ядро (nucleus accumbens), гипоталамус, гиппокамп и стриатум, в которых определена концентрацию моноаминов и их метаболитов. Интенсивные изменения наблюдались в трех структурах: префронтальная кора, прилежащее ядро и гиппокамп. Но значимые изменения были выявлены в префронтальной коре, более слабые ? в прилежащем ядре, а в гипокампе при очень интенсивных изменениях достоверность не достигалась. Такой тип реакции, возможно, связан с тем, что животных исследовали на второй день после облучения. Показано, что увеличение интервала между облучением и исследованием животных ведет к усилению эффектов радиационного воздействия. Эксперименты выявили высокую чувствительность и реактивность префронтальной коры, что мы связываем с ключевой роли этой структуры в жизненно важных процессах поведения.


85. 000617
Москвин А.Н., Лучаков Ю.И.НАПРЯЖЕНИЕ КИСЛОРОДА В МОЗГЕ КРЫС ПРИ ГИПЕРОКСИИ // Бюллетень экспериментальной биологии и медицины. 2012. Т. 154. № 10. С. 429-431.

На бодрствующих крысах Вистар были определены критические величины напряжения кислорода (Ро2) и уровень мозгового кровотока в стриатуме, при которых во время гипербарической оксигенации 5 АТА развиваются судороги. Ро2, при котором наступали судороги, соответствовало 1030±102 мм рт. ст. С помощью математической модели была выявлена зависимость Ро2 в мозге от кровотока при разных режимах гипербарической оксигенации. При сопоставлении данных эксперимента и модели показано, что судорожные дозы Ро2 могут быть достигнуты при увеличения кровотока в 1.5-3.0 раза при 4 АТА гипербарической оксигенации, в 1.2-2.0 раза -- при 5 АТА и в 0.8-1.1 раза -- при 6 АТА.


86. 000477

Окислительный стресс является важным фактором, воздействующим на различные органы при старении. Митохондрии считаются источником эндогенных оксидантов, концентрация которых может поддерживаться на низком уровне благодаря антиоксидантным ферментам. В настоящее время считается, что процессы старения тесно связаны с митохондриальной дисфункцией, одной из причин которой может быть повышение чувствительности митохондрий к активации открытия неспецифической поры (mitochondrial permeability transition pore, мРТР) во внутренней мембране митохондрий. В настоящее время широко изучается влияние природного антиоксиданта мелатонина, содержание которого в организме снижается при старении. В настоящей работе исследовали влияние мелатонина на характеристики стресс-индуцированной неселективной поры митохондрий, изолированных из крыс (старых и молодых), подверженных хронической обработке мелатонином путем орального введения. Окислительный стресс индуцировали, используя 1 и 100 мкМ гидропероксида кумола. Было обнаружено, что хроническое введение мелатонина способствовало замедлению индукции неспецифической поры в митохондриях, изолированных из старых крыс, обработанных мелатонином. При исследовании влияния гидропероксида кумола на набухание митохондрий крыс, обработанных мелатонином, было выявлено, что мелатонин способен предотвращать набухание митохондрий, стимулированное гидропероксидом кумола.


87. 000231

Изучены особенности строения тимуса и краниальных брыжеечных лимфатических узлов (ЛУ) у 72 новорождённых крыс, родившихся от самок, подвергавшихся воздействию 15% раствора этанола во время беременности (n=34), а также во время беременности и на протяжении 1 мес до ее наступления (n=38). Контролем служили 44 новорожденных животных, полученных от интактных самок. Показано, что воздействие этанола на самок только во время беременности приводит к более выраженным изменениям в брыжеечных ЛУ потомства, чем в тимусе. Они проявляются уменьшением количества ЛУ, площади их сечения, доли клеток лимфоидного ряда, подавлением митотической активности, возрастанием содержания ретикулярных клеток и усилением макрофагальной реакции. Прегравидарная алкогольная интоксикация матерей в течение 1 мес в сочетании с воздействием этанола во время беременности в большей степени влияет на морфогенез тимуса потомства, что выражается в снижении показателей его абсолютной и относительной массы, пролиферативной активности, усилении клеточной гибели, появлении микроциркуляторных и диспластических изменений


88. 000617
Рыжавский Б.Я., Задворная О.В. ВЛИЯНИЕ ГОНАДЭКТОМИИ КРЫС НА АКТИВНОСТЬ 3B-ГИДРОКСИСТЕРОИДДЕГИДРОГЕНАЗЫ В НЕЙРОНАХ НЕКОТОРЫХ ОТДЕЛОВ ГОЛОВНОГО МОЗГА // Бюллетень экспериментальной биологии и медицины. 2012. Т. 153. № 5. С. 748-750.

3b-Гидроксистероиддегидрогеназа -- ключевой фермент в синтезе стероидных гормонов в стероидпродуцирующих органах, в том числе в головном мозге, синтезирующем нейростероиды. Активность 3b-гидроксистероиддегидрогеназы может рассматриваться в качестве маркера клеток, вырабатывающих стероидные гормоны. Представлены результаты гистохимического выявления данного фермента в неокортексе, гиппокампе, коре мозжечка крыс препубертатного периода, подвергнутых гонадэктомии. Положительная реакция наблюдалась в нейронах гиппокампа и ганглиозного слоя коры мозжечка (клетках Пуркинье) а также в небольшом числе нейронов неокортекса крыс обоих полов. Гонадэктомия приводила к достоверному увеличению активности фермента в нейронах неокортекса (слой V) и гиппокампа и не отразилась на интенсивности реакции в клетках Пуркинье.


89. 010322

В мозге крыс Вистар с высокой и низкой двигательной активностью в “открытом поле” количественными цитохимическими методами исследовали активность глюкозо-6-фосфатдегидрогеназы в нейронах слоев III и V сенсомоторной коры, хвостатого ядра, прилежащего ядра, гиппокампа (поле СА 3) при длительном введении L-ДОФА и после его отмены. Ее изменения сравнивали с изменениями активности глутаматдегидрогеназы в тех же условиях. Было выявлено, что у крыс с высокой двигательной активностью после введения L-ДОФА уровень глюкозо-6-фосфатдегидрогеназы и глутаматдегидрогеназы увеличивается в стриатуме, а их изменения в сенсомоторной коре разнонаправлены. После отмены L-ДОФА показатели активности ферментов в мозге этих крыс соответствуют норме. У крыс с низкой локомоцией после введения L-ДОФА глюкозо-6-фосфатдегидрогеназа активируется в стриатуме (прилежащее ядро), глутаматдегидрогеназа в стриатуме тормозится, но активируется в гиппокампе. После отмены L-ДОФА в мозге этих крыс выявлено торможение глюкозо-6-фосфатдегидрогеназы в сенсомоторной коре (слой V) и активация глутаматдегидрогеназы в хвостатом ядре. Таким образом, показано, что ответная реакция окислительного обмена мозга на гиперфункцию дофаминергической системы зависит от индивидуальных особенностей животных, проявляющихся в их внешнем поведении, в частности в двигательной активности.


90. 010680
Сибаров Д.А., Абушик П.А., Большаков А.Е., Карелина Т.В., Кривой И.И., Антонов С.М. ЭПИЛЕПТИФОРМНЫЕ ПОСТСИНАПТИЧЕСКИЕ ТОКИ В ПЕРВИЧНОЙ КУЛЬТУРЕ НЕЙРОНОВ КОРЫ ГОЛОВНОГО МОЗГА КРЫСЫ: КАЛЬЦИЕВЫЕ МЕХАНИЗМЫ РЕГУЛЯЦИИ // Биологические мембраны: Журнал мембранной и клеточной биологии. 2014. Т. 31. № 1. С. 33-43.

Показано, что первичная культура нейронов коры головного мозга крысы является удобной моделью для изучения механизмов эпилептогенеза, в частности, эпилептиформных постсинаптических токов (ЭТ), отражающих периодический массовый асинхронный выброс глутамата. Установлено, что в первичной культуре нейронов головного мозга крысы ЭТ могут генерироваться спонтанно, либо вызываться снятием магниевого блока каналов NMDA-рецепторов, а также ГАМКергического торможения. ЭТ зависят от осцилляций внутриклеточного кальция, происходящих с участием NMDA-рецепторов, причем вторичный выход кальция из внутриклеточных депо обязателен для синхронизации ЭТ. Воздействия, вызывающие кальциевую перегрузку нейронов или снижение концентрации свободного внутриклеточного кальция, подавляют генерацию ЭТ. Так, вход кальция в нейроны при гиперактивации NMDA-рецепторов или при действии кальциевого ионофора иономицина нарушал генерацию ЭТ. Аналогичное подавление ЭТ происходило при снижении концентрации внутриклеточного кальция с помощью BAPTA, загруженного в нейроны, или путем стимуляции выведения кальция Na+/Ca2+-обменником с помощью уабаина в концентрации 1 нМ. Показана также частичная зависимость ЭТ от генерации потенциалов действия. Таким образом, самоподдерживающаяся генерация ЭТ в нейронах существует только в условиях периодического обратимого повышения концентрации внутриклеточного кальция в ограниченных концентрационных рамках.


91. 010021
Сибаров Д.А., Антонов С.М. ОСОБЕННОСТИ ПОСТСИНАПТИЧЕСКИХ ТОКОВ В ПЕРВИЧНОЙ КУЛЬТУРЕ НЕЙРОНОВ КОРЫ ГОЛОВНОГО МОЗГА КРЫС // Российский физиологический журнал им. И.М. Сеченова. 2013. Т. 99. № 6. С. 763-775.

В нейронах коры головного мозга крыс в первичной культуре с 7-го по 20-й день культивирования (DIV) изучали особенности генерации постсинаптических токов. Применение специфических блокаторов постсинаптических ионных каналов показало, что с 10 DIV в нейронах генерируются все типы электрической активности, характерные для взрослой коры: спонтанные миниатюрные тормозные (мТПСТ) и возбуждающие (мВПСТ), а также гигантские возбуждающие токи и потенциалы действия (ПД). Частота мВПСТ экспоненциально росла с 7 по 20 DIV параллельно с изменением характера генерации ПД. Выявлены мВПСТ, генерируемые активацией NMDA- и AMPA- или только AMPA-рецепторов. Показана роль ингибирования пресинаптических NMDA-рецепторов ионами магния или AP5 в модуляции частоты и амплитуды мВПСТ, что является отличием культуры нейронов от срезов мозга, по-видимому связанной с отсутствием глиального контроля синаптической передачи.


92. 000477

Иccледованы cвязанные c белками динитpозильные комплекcы железа в кpови и тканяx оpганов кpыc поcле внутpивенного введения пpепаpата этиx комплекcов c лигандом глута- тионом. Изучено также влияние динитpозильныx комплекcов железа c глутатионом на уpовень окcида азота (включая его депониpованные фоpмы) в гидpофобныx облаcтяx ткани оpганов в уcловияx еcтеcтвенного кpовоcнабжения. Уcтановлено, что поcле инъекции данного пpепаpата cодеpжание cвязанныx c белками динитpозильныx комплекcов железа в кpови и оpганаx cpазу доcтигает cвоиx макcимальныx значений и далее поcтепенно cнижаетcя, что отpажает pаcпад комплекcов c выcвобождением NO, пpичем в начале опыта в оpганаx, пpинадлежащиx к малому кpугу кpовообpащения (cеpдце, легкое), и в кpови cкоpоcти такого падения cущеcтвенно выше, чем в печени и почкаx. Методом cпиновыx ловушек показано, что динитpозильные комплекcы железа c глутатионом, как иcточник депониpованныx фоpм NO, включая S-нит- pозотиолы, дейcтвуют в уcловияx еcтеcтвенного кpовоcнабжения более избиpательно на cеp- дечную мышцу, чем на дpугие иccледованные оpганы.


93. 010322

Проведено исследование моторных реакций у крыс с наследственной кататонией (линия ГК) в неонатальный период онтогенеза. Крысята линии ГК отличались от контрольных крысят Вистар большей долей дискинетических движений и поз в 1?2 дни неонатального периода и меньшим числом двигательных актов в последующие дни развития. Обнаружен повышенный по сравнению с контролем уровень норадреналина на 7-й, 10-й, 14-й дни в полушариях и на 10-й день в стволе мозга. Количество серотонина у крыс линии ГК было снижено в полушариях мозга на 1-й и 14-й дни и в стволе мозга на 14-й день. Также показан более низкий уровень 5-ГИУК в стволе мозга на 1-й и 7-й дни у крыс кататонической линии по сравнению с контрольной группой Вистар. Обсуждены сравнительные характеристики медиаторных механизмов на селекционной модели крыс линии ГК, фармакологических моделях in vivo и спинно-мозговых препаратах in vitro в раннем онтогенезе.


94. 001075

На основе гибридов инбредной линий крыс Крушинского-Молодкиной (КМ) с высокой предрасположенностью к аудиогенной эпилепсии (АЭ) и крыс Вистар, не предрасположенных к АЭ, проводится селекция на признак “отсутствие предрасположенности к АЭ. Создание линии, близкой по генотипу к линии КМ, в которой значимую долю составляют животные, не предрасположенные к АЭ, важно для более корректного использования линии КМ как генетической модели судорожных состояний. Поскольку аллели, определяющие предрасположенность к АЭ, рецессивны, отбор на противоположный признак идет неизбежным образом медленно.


95. 000231

Cинаптогенез в nucleus raphes dorsalis (NRD) продолговатого мозга крыс Вистар изучен в конце пренатального (19-еи 20-е сутки) и раннего постнатального (5-еи 20-е сутки) периодов (по 8–10 животных на временную точку), а также исследована роль серотонина в формировании синаптических контактов в этот период развития. Показано, что у контрольных (интактных) животных на 19-е сутки пренатального развития в NRD-d, NRD-v и NRD-l начинает формироваться нейропиль, и на отростках появляются синаптические контакты, а на 20-е сутки они впервые обнаруживаются на поверхности тел нейронов. Плотность расположения синаптофизин-положительных гранул как на отростках в нейропиле, так и на телах нейронов, резко и значительно возрастает к 5-м суткам постнатального развития. В дальнейшем до 20-х суток ее увеличение незначительно. Дефицит серотонина во второй половине внутриутробного развития, вызванный введением пара-хлорфенилаланина самкам на 16-е сутки беременности, приводит к значительной задержке синаптогенеза в NRD у их потомства как в пре-, так и в ранний постнатальный периоды. С увеличением постнатального возраста плотность расположения синаптических контактов увеличивается не одинаково в разных частях NRD: в NRD-d она приближается к контрольной, ав NRD-v и NRD-l — остается сниженной. Полученные результаты свидетельствуют об участии серотонина в синаптогенезе в NRD.


96. 010322
Шерстнев В.В., Голубева О.Н., Грудень М.А., Сторожева З.И., Гусева Е.В. НЕЙРОГЕНЕЗ И НЕЙРОАПОПТОЗ В РАЗЛИЧНЫХ ОТДЕЛАХ ЗРЕЛОГО МОЗГА КРЫС WISTAR // Нейрохимия. 2012. Т. 29. № 3. С. 206-212.

Исследованы особенности нейрогенеза в различных отделах головного мозга, ассоциированных с механизмами обучения и памяти у взрослых крыс Wistar. На срезах головного мозга с помощью метода иммунофлюоресценции в зубчатой фасции и полях СА1-СА4 гиппокампа, различных зонах церебральной коры и черве мозжечка определяли число позитивно окрашенных на BrdU (маркер пролиферации клеток) клеток через 24 ч, 15 и 30 сут после его введения. Используя двойное окрашивание в указанных структурах мозга и временных точках, проводили подсчет численности вновь образованных клеток, которые экспрессируют нейрональный (NeuN) или астроцитарный (GAFP), а также апоптотический (ApoDNA) маркеры. Обнаружено, что во всех изученных отделах мозга образуются клетки, которые дифференцируются в нейроны и астроциты, при этом имеются значимые региональные различия выраженности и динамики пролиферации, дифференцировки и апоптотической гибели вновь образованных клеток. Обсуждаются возможные причины количественных различий между выявленными в работе и полученными ранее другими исследователями показателями нейрогенеза/нейроапоптоза у взрослых крыс Wistar.


97. 010322
Шерстнев В.В., Грудень М.А., Александров Ю.И., Сторожева З.И., Голубева О.Н., Прошин А.Т. РАЗЛИЧНЫЕ ПОПУЛЯЦИИ НЕЙРОНОВ РЕЛЕВАНТНЫХ СТРУКТУР МОЗГА КРЫС ИЗБИРАТЕЛЬНО ВОВЛЕКАЮТСЯ В ОБЕСПЕЧЕНИЕ ПРОЦЕССОВ ДОЛГОВРЕМЕННОЙ ПРОСТРАНСТВЕННОЙ ПАМЯТИ Шерстнев В.В., Грудень М.А., Александров Ю.И., Сторожева З.И., Голубева О.Н., Прошин А.Т. Нейрохимия. 2013. Т. 30. № 4. С. 314-320.

С помощью иммуногистохимического метода исследовали экспрессию транскрипционного фактора c-fos в клетках, синтезирующих нейронспецифические белки NeuN и калбиндин D-28K в гиппокампе, черве мозжечка, моторной и ретроспениальной коре мозга крыс после обучения навыку нахождения скрытой платформы в водном лабиринте. Выявляли также апоптотические нервные клетки экспрессирующие NeuN. Обнаружены значимые различия внутри и межструктурного распределения NeuN и калбиндин-позитивных нейронов, экспрессирующих c-fos у обученных и контрольных животных. Выявлена взаимосвязь количества экспрессирующих c-fos нейронов, меченных NeuN в ретроспениальной коре мозга, с показателями упрочения долговременной пространственной памяти. Предполагается, что полученные результаты свидетельствуют об избирательном вовлечении нервных клеток различных популяций нейронов, локализующихся в релевантных структурах головного мозга крыс в обеспечение процессов долговременной пространственной памяти.


98. 000617
Шубенина Е.В., Кудрин В.С., Клодт П.М., Наркевич В.Б., Кузнецова Е.А., Гудашева Т.А., Островская Р.У. ВЛИЯНИЕ ДИПЕПТИДНОГО АНАЛОГА НЕЙРОТЕНЗИНА ДИЛЕПТА НА МЕТАБОЛИЗМ И СИНТЕЗ ДОФАМИНА В ПРИЛЕЖАЩЕМ ЯДРЕ МОЗГА КРЫС ВИСТАР // Бюллетень экспериментальной биологии и медицины. 2012. Т. 153. № 5. С. 649-652.

Изучали влияние дипептидного аналога нейротензина Дилепта (N-капроил-L-пролил-L-тирозина метилового эфира) на метаболизм и синтез дофамина в прилежащем ядре мозга крыс Вистар. Показано, что Дилепт повышает уровень дофамина и его метаболитов гомованилиновой кислоты и диоксифенилаланина, а также ускоряет оборот дофамина в этой структуре. Установлено, что в условиях блокады импульсной активности дофаминергических нейронов, вызванной введением гамма-бутиролактона в сочетании с угнетением декарбоксилазы ароматических кислот, обусловленным введением 3-оксибензилгидразина, Дилепт повышает скорость синтеза дофамина. Выявленный спектр фармакологической активности Дилепта в отношении дофаминергической системы прилежащего ядра сходен с характерным для атипичных нейролептиков и эндогенного антипсихотика нейротензина.


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