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Новые достижения в иммунной и репродуктивной системе крыс

Журнальные статьи

1. PDF
Ahsan N. et al. Comparative effects of Bisphenol S and Bisphenol A on the development of female reproductive system in rats; a neonatal exposure study // Chemosphere. 2018. Vol. 197. P. 336–343.

Bisphenol A (BPA) has been well documented for its endocrine disrupting potential however, very little is known about endocrine disrupting abilities of bisphenol S (BPS). The present study aimed to compare the endocrine disrupting potentials of BPS with BPA, using female rats as an experimental animal model. On postnatal day 1 (PND 1) female pups born were randomly assigned to seven different treatments. Control group received subcutaneous injection of castor oil (50 mu l) from PND 1 to PND 10. Three groups of female pups were injected subcutaneously with different concentrations (0.5, 5 and 50 mg/kg in 50 mu l castor oil) of BPS, while remaining three groups were treated with 0.5, 5 and 50 mg/kg BPA. Highest doses treatments of both compounds resulted in delayed puberty onset and altered estrous cyclicity. Final body weight was significantly high in the highest dose treated groups of both BPS and BPA. Gonadosomatic index, absolute and relative weight of uteri was significantly reduced in BPS (5 and 50 mg/kg) and BPA (5 and 50 mg/kg) treated groups than control. Plasma concentrations of testosterone and estradiol were significantly increased, while plasma progesterone, Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) concentrations were significantly reduced in highest doses treated groups. Dose dependent increase in the number of cystic follicles in the ovaries was evident along with an increase in the number of atratic follicles. The results suggest that neonatal exposure to higher concentrations of BPS can lead to BPA like structural and endocrine alterations in female rats. (C) 2018 Elsevier Ltd. All rights reserved.

http://dx.doi.org/10.1016%2Fj.chemosphere.2017.12.118

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Almahozi A. et al. Retrieval-Induced Forgetting in a Pentylenetetrazole-Induced Epilepsy Model in the Rat // Brain Sci. 2018. Vol. 8, № 12. P. 215.

The selective retrieval of some information may lead to the forgetting of related, but non-retrieved information. This memory phenomenon is termed retrieval-induced forgetting (RIF). Active inhibition is thought to function to resolve interference from competing information during retrieval, which results in forgetting. Epilepsy is associated with impaired inhibitory control that contributes to executive dysfunction. The purpose of this study is to investigate whether rats in a kindling model of epilepsy demonstrate normal levels of RIF. Rats were divided into two groups: saline and kindling. Pentylenetetrazole was injected intraperitoneally until the rats kindled. RIF was tested using a modified version of the spontaneous object recognition test, consisting of a sample phase, retrieval or interference phase, and a test phase. Exploration time for each object was analyzed. RIF was demonstrated in the saline group when rats subjected to the retrieval phase failed to discriminate between the familiar object and the novel object later in the test phase. Kindled rats, on the other hand, did not suffer forgetting even when they were subjected to the retrieval phase, as they spent significantly longer times exploring the novel rather than the familiar object in the test phase. Therefore, RIF was not observed in the kindling group. These findings indicate impaired retrieval-induced forgetting in kindled rats, which may be suggestive of a deficit in the inhibitory control of memory.

http://dx.doi.org/10.3390%2Fbrainsci8120215

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Al-Otaish H. et al. Relationship between absolute and relative ratios of glutamate, glutamine and GABA and severity of autism spectrum disorder // Metab. Brain Dis. 2018. Vol. 33, № 3. P. 843–854.

Autism spectrum disorder (ASD) is a neurodevelopmental pathology characterized by an impairment in social interaction, communication difficulties, and repetitive behaviors. Glutamate signaling abnormalities are thought to be considered as major etiological mechanisms leading to ASD. The search for amino-acidic catabolytes related to glutamate in patients with different levels of ASD might help current research to clarify the mechanisms underlying glutamate signaling and its disorders, particularly in relation to ASD. In the present study, plasma levels of the amino acids and their derivatives glutamate, glutamine, and gamma-aminobutyric acid (GABA), associated with their relative ratios, were evaluated using an enzyme-linked immunosorbent assay (ELISA) technique in 40 male children with ASD and in 38 age- and gender-matched neurotypical health controls. The Social Responsiveness Scale (SRS) was used to evaluate social cognition, and the Childhood Autism Rating Scale (CARS) was used to assess subjects' behaviors. Children with ASD exhibited a significant elevation of plasma GABA and glutamate/glutamine ratio, as well as significantly lower levels of plasma glutamine and glutamate/GABA ratios compared to controls. No significant correlation was found between glutamate levels and the severity of autism, measured by CARS and SRS. In receiver operating characteristic (ROC) curve analysis, the area under the curve for GABA compared to other parameters was close to one, indicating its potential use as a biomarker. Glutamine appeared as the best predictive prognostic markers in the present study. The results of the present study indicate a disturbed balance between GABAergic and glutamatergic neurotransmission in ASD. The study also indicates that an increased plasma level of GABA can be potentially used as an early diagnostic biomarker for ASD.

http://dx.doi.org/10.1007%2Fs11011-018-0186-6

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Araujo Leite G.A. et al. Reproductive outcomes in rat female offspring from male rats co-exposed to rosuvastatin and ascorbic acid during pre-puberty // J. Toxicol. Env. Health Part A. 2018. Vol. 81, № 17. P. 873–892.

Dyslipidemias are occurring earlier in different countries due to the increase of obesity, bad eating habits, and sedentary lifestyle. Rosuvastatin reduces serum cholesterol; however, several studies associated statin exposure with male reproduction impairment. Ascorbic acid (AA) is an antioxidant substance that plays a protective role in the male reproductive system. Male rats were randomly divided into 6 experimental groups (n=10), which received saline solution 0.9%, 3 or 10mg/kg/day of rosuvastatin, 150mg/day of AA or 3 or 10mg/kg/day of rosuvastatin associated with 150mg/day of AA from post-natal day (PND) 23 until PND 53. On PND 100, males were mated with non-treated female rats to obtain the female pups. The day of vaginal opening and the first estrus were assessed in the offspring. Two sets of females were euthanized on the first estrus after PND 42 and PND 75 to evaluate the histology of reproductive organs and hormone levels. A third set was used for sexual behavior and fertility test around PND 75. Female offspring from males exposed or co-exposed to the higher dose of statinexhibited a lower number of corpora lutea during puberty. On sexual maturity, the experimental group from males that were exposed to 3mg displayed lower uterine luminal epithelium area. Paternal exposure to rosuvastatin at pre-puberty diminished uterine luminal epithelium in female offspring suggesting epigenetic changes were initiated by statin. Ascorbic acid co-administered to pre-pubertal males was able to ameliorate the reproductive damage in rat female offspring in adulthood.

http://dx.doi.org/10.1080%2F15287394.2018.1504702

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Chehrei S. et al. Pentoxifylline besides naltrexone recovers morphine-induced inflammation in male reproductive system of rats by regulating Toll-like receptor pathway // Andrologia. 2017. Vol. 49, № 9. P. e12749.

This study aimed to investigate the effect of pentoxifylline on complications of prolonged usage of morphine upon the testis and sperm parameters of rats. In this study, forty male Wistar rats were divided into five groups (n = 8) and treated for 56 days to only saline, only morphine, only pentoxifylline, pentoxifylline + morphine and naltrexone + morphine. The diameters of seminiferous tubules, the maturity of germ line epithelium and sperm parameters were evaluated. The expression of inflammatory-related factors in testis tissues were also investigated at gene and protein levels. The data were calculated by one-way ANOVA test followed by Tukey's post hoc test using SPSS software for windows (version 20). Seminiferous tubule diameter, the maturity of spermatogonia and sperm parameters were significantly decreased in morphine group in comparison with control, pentoxifylline and pentoxifylline + morphine groups (p < .001). The expression of anti-inflammatory markers, at both gene and protein levels, was significantly increased in testis of morphine-treated rats in comparison with other groups (p < .001). Chronic morphine administration induces destructive effects on male reproductive system by regulating inflammatory responses. Pentoxifylline recovers the destructive effects of morphine on male reproductive system by inhibiting TLR (Toll-like receptor) activity, as an anti-inflammatory response.

http://dx.doi.org/10.1111%2Fand.12749

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De Felice M. et al. The PPAR alpha agonist fenofibrate attenuates disruption of dopamine function in a maternal immune activation rat model of schizophrenia // CNS Neurosci. Ther. 2019. Vol. 25, № 5. P. 549–561.

Aims Prenatal maternal immune activation (MIA) is associated with a risk to develop schizophrenia and affects dopamine systems in the ventral tegmental area (VTA), key region in the neurobiology of psychoses. Considering the well-described sex differences in schizophrenia, we investigated whether sex affects MIA impact on dopamine system and on schizophrenia-related behavioral phenotype. Furthermore, considering peroxisome proliferator-activated receptor-alpha (PPAR alpha) expression in the CNS as well as its anti-inflammatory and neuroprotective properties, we tested if PPAR alpha activation by prenatal treatment with a clinically available fibrate (fenofibrate) may mitigate MIA-related effects. Methods We induced MIA in rat dams with polyriboinosinic-polyribocytidylic acid (Poly I:C) and assessed prepulse inhibition and dopamine neuron activity in the VTA by means of electrophysiological recordings in male and female preweaned and adult offspring. Results Poly I:C-treated males displayed prepulse inhibition deficits, reduced number and firing rate of VTA dopamine neurons, and paired-pulse facilitation of inhibitory and excitatory synapses. Prenatal fenofibrate administration attenuated detrimental effects induced by MIA on both the schizophrenia-like behavioral phenotype and dopamine transmission in male offspring. Conclusion Our study confirms previous evidence that females are less susceptible to MIA and highlights PPAR alpha as a potential target for treatments in schizophrenia.

http://dx.doi.org/10.1111%2Fcns.13087

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Deng J.V. et al. MeCP2 Expression in a Rat Model of Risky Decision Making // Neuroscience. 2018. Vol. 369. P. 212–221.

Many neuropsychiatric disorders are associated with abnormal decision making involving risk of punishment, but the underlying molecular basis remains poorly understood. Methyl CpG-binding protein 2 (MeCP2) is an epigenetic factor that regulates transcription by directly binding to methylated DNA. Here, we evaluated MeCP2 expression in the context of risk-taking behaviors using the Risky Decision-making Task (RDT), in which rats make discrete choices between a small "safe" food reward and a large "risky" food reward accompanied by varying probabilities of punishment. In Experiment 1, expression of MeCP2 as assessed by immunoblotting in the medial prefrontal cortex (mPFC), but not the striatum, was inversely correlated with the degree of preference for the large, risky reward (risk taking) seven days after the last RDT test. In Experiment 2, MeCP2 expression 90 min after RDT testing, assessed using immunohistochemistry, was suppressed in both the dorsal mPFC (dmPFC) and nucleus accumbens compared to home cage controls, indicating that MeCP2 expression is modulated by RDT performance. Additional experiments revealed that RDT performance increased expression of MeCP2 phosphorylated at Ser421 (associated with neuronal activity and activation of gene expression) in dmPFC principal neurons. Finally, as in Experiment 1, lower expression of MeCP2 in the ventral mPFC was associated with greater risk taking under baseline conditions. Together, these findings indicate a complex regulatory role of MeCP2 in risky decision making, and suggest that epigenetic factors may be an important component of the molecular mechanisms underlying such decision-making processes. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

http://dx.doi.org/10.1016%2Fj.neuroscience.2017.11.016

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Donaldson T.N. et al. Progression and stop organization reveals conservation of movement organization during dark exploration across rats and mice // Behav. Processes. 2019. Vol. 162. P. 29–38.

Spatial orientation is a ubiquitous feature of animal behavior. Environmental and self-movement cues are sources of information used to maintain spatial orientation. The literature has typically focused on differences between mice and rats using environmental cues to guide movement. The current study uses the organization of exploratory behavior under dark conditions to investigate species differences in self-movement cue processing. Mouse and rat exploratory behavior was recorded under dark conditions on a circular table without walls. The resulting movements were segmented in progressions (movement >= 3 cm/s) and stops (movement < 3 cm/s). Mice exhibited longer travel distances, faster progression peak speeds, and weaker tendency to scale progression peak speeds to Euclidean distances relative to rats. In contrast, similar levels of performance were observed on measures (progression path circuity, change in heading, stability of stopping behavior) sensitive to vestibular pathology. These results are consistent with species differences in a variety of performance variables; however, self-movement cue based spatial orientation did not differentiate between mice and rats. This work establishes a translational foundation for future work investigating the neurobiology of self-movement cue processing using species-unique neuroscience techniques.

http://dx.doi.org/10.1016%2Fj.beproc.2019.01.003

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dos Santos T.G., Leivas Pereira M.S., Oliveira D.L. Rat Cerebrospinal Fluid Treatment Method through Cisterna Cerebellomedullaris Injection // Neurosci. Bull. 2018. Vol. 34, № 5. P. 827–832.

Drugs that lack the ability to cross the blood-brain barrier (BBB) need to be placed directly into the central nervous system. Our laboratory studies the involvement of the glutamatergic system in the aggressiveness of glioma, and some ligands of glutamate receptors cannot permeate the BBB. Here, glioma-implanted rats were treated by a technique that delivers ligands directly into the cerebrospinal fluid by puncture into the cisterna cerebellomedullaris. Rats were anesthetized and fixed in a rodent stereotactic device. The head was gently tilted downwards at an angle that allowed exposure of the cisterna. Injection into the cisterna was done freehand using a gingival needle coupled to a microsyringe. The efficiency of intracisternal injection was demonstrated using a methylene blue solution. This type of injection is adaptable for any rodent model using small volumes of a variety of other drugs, and is an interesting method for neuroscience studies.

http://dx.doi.org/10.1007%2Fs12264-018-0223-9

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Fathi N. et al. The effect of silver nanoparticles on the reproductive system of adult male rats: A morphological, histological and DNA integrity study // Adv. Clin. Exp. Med. 2019. Vol. 28, № 3. P. 299–305.

Background. Silver nanoparticles (AgNPs) are more often used in various products, and consequently the potential deleterious effects associated with exposure to them are of concern. Several lines of evidence have demonstrated that the toxicity of AgNPs affects different organs and leads to some side effects, including weight loss, inflammation and cell death. Objectives. The aim of this study was to evaluate the effect of different concentrations of AgNPs on sperm parameters and testicular histology. Material and methods. In the present study, 28 male adult Wistar rats were categorized into a control group and 3 experimental groups (AgNP-1, AgNP-2 and AgNP-3), intraperitoneally (i.p.) receiving 30, 125 and 300 mg/kg of AgNPs, respectively. Twenty-eight days after injection the epididymes and the testes of each rat were dissected in order to evaluate sperm parameters, sperm chromatin integrity and histomorphometric changes in the testicular tissue. Results. The results showed a significant decrease in sperm count (p < 0.0001), vitality (p < 0.05) and morphology changes (p < 0.001) in the group receiving 300 mg/kg of AgNPs compared to the control group. A significant decrease was also observed in the number of spermatogonia, Sertoli and Leydig cells in the AgNP-2 and AgNP-3 groups (p < 0.05). The evaluation of sperm chromatin did not show any significant differences among the experimental groups (p > 0.05). Conclusions. The data showed some dose-dependent adverse effects of AgNPs on sperm and seminiferous tubules. More experimental investigations are necessary to draw better conclusions regarding the safety of nanoparticles (NPs) on the male reproduction system.

http://dx.doi.org/10.17219%2Facem%2F8160

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Foldi C.J., Milton L.K., Oldfield B.J. The Role of Mesolimbic Reward Neurocircuitry in Prevention and Rescue of the Activity-Based Anorexia (ABA) Phenotype in Rats // Neuropsychopharmacology. 2017. Vol. 42, № 12. P. 2292–2300.

Patients suffering from anorexia nervosa (AN) become anhedonic; unable or unwilling to derive normal pleasures and avoid rewarding outcomes, most profoundly in food intake. The activity-based anorexia (ABA) model recapitulates many of the characteristics of the human condition, including anhedonia, and allows investigation of the underlying neurobiology of AN. The potential for increased neuronal activity in reward/hedonic circuits to prevent and rescue weight loss is investigated in this model. The mesolimbic pathway extending from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) was activated using a dual viral strategy, involving retrograde transport of Cre (CAV-2-Cre) to the VTA and coincident injection of DREADD receptors (AAV-hSyn-DIO-hM3D(Gq)-mCherry). Systemic clozapine-n-oxide (CNO; 0.3 mg/kg) successfully recruited a large proportion of the VTA-NAc dopaminergic projections, with activity evidenced by colocalization with elevated levels of Fos protein. The effects of reward circuit activation on energy balance and predicted survival was investigated in female Sprague-Dawley rats, where free access to running wheels was paired with time-limited (90 min) access to food, a paradigm (ABA) which will cause anorexia and death if unchecked. Excitation of the reward pathway substantially increased food intake and food anticipatory activity FAA) to prevent ABA-associated weight loss, while overall locomotor activity was unchanged. Similar activation of reward circuitry, delayed until establishment of the ABA phenotype, rescued rats from their precipitous weight loss. Although these data are consistent with shifts primarily in food intake, the contribution of mechanisms including energy expenditure to survival remains to be determined. These results will inform the neurobiological underpinnings of AN, and provide insight into the mechanisms of reward circuitry relevant to feeding and weight loss.

http://dx.doi.org/10.1038%2Fnpp.2017.63

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Goode T.D., Holloway-Erickson C.M., Maren S. Extinction after fear memory reactivation fails to eliminate renewal in rats // Neurobiol. Learn. Mem. 2017. Vol. 142. P. 41–47.

Retrieving fear memories just prior to extinction has been reported to effectively erase fear memories and prevent fear relapse. The current study examined whether the type of retrieval procedure influences the ability of extinction to impair fear renewal, a form of relapse in which responding to a conditional stimulus (CS) returns outside of the extinction context. Rats first underwent Pavlovian fear conditioning with an auditory CS and footshock unconditional stimulus (US); freezing behavior served as the index of conditioned fear. Twenty-four hours later, the rats underwent a retrieval-extinction procedure. Specifically, 1 h prior to extinction (45 CS-alone trials; 44 for rats receiving a CS reminder), fear memory was retrieved by either a single exposure to the CS alone, the US alone, a CS paired with the US, or exposure to the conditioning context itself. Over the next few days, conditional freezing to the extinguished CS was tested in the extinction and conditioning context in that order (i.e., an ABBA design). In the extinction context, rats that received a CS + US trial before extinction exhibited higher levels of conditional freezing than animals in all other groups, which did not differ from one another. In the renewal context, all groups showed renewal, and none of the reactivation procedures reduced renewal relative to a control group that did not receive a reactivation procedure prior to extinction. These data suggest retrieval-extinction procedures may have limited efficacy in preventing fear renewal. (C) 2017 Elsevier Inc. All rights reserved.

Inhttp://dx.doi.org/10.1016%2Fj.nlm.2017.03.001,

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Hei M. et al. Effects of chronic mild stress induced depression on synaptic plasticity in mouse hippocampus // Behav. Brain Res. 2019. Vol. 365. P. 26–35.

Chronic mild stress (CMS) model is most similar to the depression human suffered in daily life. Strong evidence proved the important role of hippocampal synaptic plasticity in the mechanism of depression. This study investigated the effect of CMS on synaptic plasticity in hippocampus. Our results showed that CMS impaired spatial memory and exploring ability, disturbed the release of neurotransmitters including 5-hydroxytryptamine (5-HT) and dopamine (DA), reduced the density of synaptic vesicle in inner molecular layer, increased the number of thin spines in inner and outer molecular layer, whereas did not affect the density of spine apparatus, the above mentioned were probably related to the reduction of astrocytes and activation of microglial cells.

http://dx.doi.org/10.1016%2Fj.bbr.2019.02.044

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Horst C.H. et al. Signature of Aberrantly Expressed microRNAs in the Striatum of Rotenone-Induced Parkinsonian Rats // Neurochem. Res. 2018. Vol. 43, № 11. P. 2132–2140.

Parkinson's disease (PD) is a highly complex brain disorder regarding clinical presentation, pathogenesis, and therapeutics. The cardinal motor signs, i.e., rigidity, bradykinesia, and unilateral tremors, arise in consequence of a progressive neuron death during the prodromal phase. Although multiple transmission systems are involved in disease neurobiology, patients will cross the line between the prodromal and early stage of diagnosed PD when they had lost half of the dopaminergic nigrostriatal cells. As the neurons continue to die ascending the neuroaxis, patients will face a more disabling disease with motor and nonmotor signs. Shedding light on molecular mechanisms of neuron death is an urgent need for understanding PD pathogenesis and projecting therapeutics. This work examined the expression of microRNAs in the striatum of parkinsonian rats chronically exposed to rotenone (2.5mg/Kg, i.p., daily for 10 days). Rotenone caused motor deficits, the loss of TH(+) cells in the nigrostriatal pathway, and a marked microgliosis. This parkinsonian rat striatum was examined at 26 days after the last rotenone injection, for quantification of microRNAs, miR-7, miR-34a, miR-26a, miR-132, miR-382, and Let7a, by qPCR. Parkinsonian rats presented a significant increase in miR-26a and miR-34a (1.5 and 2.2 fold, respectively, P<0.05), while miR-7 (0.5 fold, P<0.05) and Let7a were downregulated. This work reports for first time microRNAs aberrantly expressed in the striatum of rotenone-induced parkinsonian rats, suggesting that this dysregulation may contribute to PD pathogenesis. Beyond revealing new clues of neurodegeneration, our findings might prime further studies targeting miRNAs for neuroprotection or even for diagnosis proposal.

http://dx.doi.org/10.1007%2Fs11064-018-2638-0

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Jing X. et al. Toxic effects of Tripterygium wilfordii Hook F on the reproductive system of adolescent male rats // Biomed. Pharmacother. 2017. Vol. 95. P. 1338–1345.

Tripterygium wilfordii Hook F. (TWHF) is a compound extracted from Lei Gong Teng (Thunder God Vine) that has been used to treat a variety of immune-related diseases in clinical practice, particularly in pediatrics. Nevertheless, clinical data indicated that glycosides from Tripterygium wilfordii Hook F (GTW) are toxic to the male reproductive system, but the mechanism is unknown. Here, the administration of a high dose of GTW for 4 weeks and a low dose for 12 weeks can reduce the body weights and testes weights in adolescent male rats. This effect is accompanied by a significantly reduction in the serum testosterone levels. Notably, short-term use of high-dose GTW or long-term use of low-dose GTW leads to testicular damage in adolescent male rats. Furthermore, the expression of the steroidogenic acute regulatory protein (StAR), P450 side chain cleavage enzyme (P450scc), cytochrome P450 17-hydroxylase (P450c17), 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) mRNAs and proteins in the testes was down-regulated by a short-term treatment with high-dose GTW and a long-term treatment with low-dose GTW. Therefore, GTW exhibit male reproductive toxicity in a concentration-and time-dependent manner by inhibiting the expression of the key enzymes and total cholesterol level involved in testosterone synthesis.

http://dx.doi.org/10.1016%2Fj.biopha.2017.09.038

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Karabulut G., Barlas N. Genotoxic, histologic, immunohistochemical, morphometric and hormonal effects of di-(2-ethylhexyl)-phthalate (DEHP) on reproductive systems in pre-pubertal male rats // Toxicol. Res. 2018. Vol. 7, № 5. P. 859–873.

Di-(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer and people are exposed to various amounts on a daily basis. This study was designed to evaluate the genotoxic, histologic, immunohistochemical, morphometric and hormonal effects of DEHP (100, 200 and 400 mg kg(-1) per day DEHP) administered daily to rats by oral gavage for 28 days. The rats were divided into five groups including oil control, positive control (MMS) and treatment groups (100, 200 and 400 mg kg(-1) per day DEHP). They were euthanized at the end of the experiment, organ and body weights were recorded and serum was collected for biochemical and hormone analysis. The genotoxic effect was measured in blood and sperm using the Comet assay. The testes, epididymis, prostate gland and seminal vesicle were collected and stained with hematoxylin and eosin for histopathologic analysis. Epithelial height, luminal and tubular diameters (M) in seminiferous tubules were also measured. Moreover, the study revealed an increase in the DNA damage level in both blood lymphocytes and sperm. At the end of the experiment, the tail intensity showed a significant increase in the 100 mg kg(-1) per day (p = 0.032), 200 mg kg(-1) per day (p = 0.019) and 400 mg kg(-1) per day (p = 0.012) dose groups compared to the control group in blood. Furthermore, testosterone was decreased in all treatment groups compared to the control group. Besides, DEHP caused a significant decrease in the leukocyte levels (p = 0.017) and hemoglobin content, as well as an increased mean cell volume (MCV) count (p = 0.029) in the 400 mg kg(-1) per day group when compared to the control values. It is important to indicate that there were apoptotic cells seen in the lumen of testes in the 200 and 400 mg kg(-1) per day dose groups using the Tunel method. Therefore, with this study, it has been illustrated that DEHP caused DNA damage in blood and sperm and concrete negative effects on the reproductive system in rats from the pre-pubertal period to the pubertal period. This is a unique study since there has not been any other study that presents the indicated level of DNA damage while considering the genotoxic, histologic, immunohistochemical, morphometric and hormonal effects of DEHP.

http://dx.doi.org/10.1039%2Fc8tx00045j

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Kaya K. et al. Favourable effect of beta-glucan treatment against cisplatin-induced reproductive system damage in male rats // Andrologia. P. e13342.

The aim of this study was to investigate the potential beneficial effects of beta-glucan treatment against oxidative, histological and spermatological damage caused by cisplatin on the male reproductive system. Twenty-eight Sprague Dawley male rats were used in the study. The rats were randomly divided into four equal-sized groups: a control group, cisplatin group (7 mg/kg in a single-dose cisplatin administered intraperitoneally), beta-glucan group (beta-glucan given at a dose of 50 mg kg(-1) d(-1) for 14 day) and a cisplatin plus beta-glucan group (cisplatin and beta-glucan administered together at the same dose). Cisplatin administration induced an increase in the level of thiobarbituric acid-reactive substances, a lipid peroxidation indicator. It induced a decrease in enzymatic (superoxide dismutase, catalase and glutathione peroxidase) activities and nonenzymatic (reduced glutathione) antioxidant levels. In addition, cisplatin caused both histological and spermatological damage, as shown by a decrease in sperm motility and epididymal sperm concentrations and an increase in abnormal sperm rates. The beta-glucan treatment improved cisplatin-induced oxidative, histological and spermatological damage. This study revealed that beta-glucan treatment provided prevention against male reproductive system damage caused by cisplatin. These preventative effects were likely due to its antioxidant properties.

http://dx.doi.org/10.1111%2Fand.13342

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Kuiper L.B. et al. Drug-taking in a socio-sexual context enhances vulnerability for addiction in male rats // Neuropsychopharmacology. 2019. Vol. 44, № 3. P. 503–513.

Vulnerability to develop addiction is influenced by numerous factors, including social behavior. Specifically, in human users, drug taking in a socio-sexual context appears to enhance further drug-seeking behavior. Users report heightened sexual pleasure as a motivation for further drug use and display risk behaviors even when tested in drug-free state. Here, using a preclinical model of limited voluntary drug use in rats, the hypothesis was tested that methamphetamine (Meth)-taking concurrently with socio-sexual experience increases vulnerability to addiction. Male Sprague Dawley rats were socially housed and underwent limited-access Meth self-administration (maximum 1 mg/kg/session). Meth-taking was either concurrent or non-concurrent with sexual behavior: concurrent animals were mated with a receptive female immediately after each session, while non-concurrent animals gained equivalent sexual experience the week prior. Next, drug-seeking behaviors were measured during cue reactivity, extinction, and reinstatement sessions using different extinction and reinstatement protocols in 4 separate studies. Both groups equally acquired Meth self-administration and did not differ in total Meth intake. However, drug-seeking behavior was significantly higher in concurrent animals during cue reactivity tasks, extinction sessions, and cue-or Meth-induced reinstatement tests. In addition, sexual behavior in the absence of Meth triggered reinstatement of drug-seeking in concurrent animals. These results indicate that Meth-taking in a socio-sexual context significantly enhances vulnerability for drug addiction in male rats. This preclinical paradigm of drug self-administration concurrent with socio-sexual behavior provides a useful model for studying the underlying neurobiology of socially driven vulnerability to drug addiction.

http://dx.doi.org/10.1038%2Fs41386-018-0235-1

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Lai S. et al. Toxic effect of acrylamide on the development of hippocampal neurons of weaning rats // Neural Regen. Res. 2017. Vol. 12, № 10. P. 1648–1654.

Although numerous studies have examined the neurotoxicity of acrylamide in adult animals, the effects on neuronal development in the embryonic and lactational periods are largely unknown. Thus, we examined the toxicity of acrylamide on neuronal development in the hippocampus of fetal rats during pregnancy. Sprague-Dawley rats were mated with male rats at a 1: 1 ratio. Rats were administered 0, 5, 10 or 20 mg/kg acrylamide intragastrically from embryonic days 6-21. The gait scores were examined in pregnant rats in each group to analyze maternal toxicity. Eight weaning rats from each group were also euthanized on postnatal day 21 for follow-up studies. Nissl staining was used to observe histological change in the hippocampus. Immunohistochemistry was conducted to observe the condition of neurites, including dendrites and axons. Western blot assay was used to measure the expression levels of the specific nerve axon membrane protein, growth associated protein 43, and the presynaptic vesicle membrane specific protein, synaptophysin. The gait scores of gravid rats significantly increased, suggesting that acrylamide induced maternal motor dysfunction. The number of neurons, as well as expression of growth associated protein 43 and synaptophysin, was reduced with increasing acrylamide dose in postnatal day 21 weaning rats. These data suggest that acrylamide exerts dose-dependent toxic effects on the growth and development of hippocampal neurons of weaning rats.

http://dx.doi.org/10.4103%2F1673-5374.217345

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Liu X. et al. Effects of oral cimetidine on the reproductive system of male rats // Exp. Ther. Med. 2018. Vol. 15, № 6. P. 4643–4650.

Cimetidine is widely used for the treatment of digestive tract ulcers, but it induces testis injury. To explore the mechanisms underlying cimetidine-induced toxicity towards the testis, the effects of oral cimetidine on the reproductive system of male rats were assessed. Cimetidine was orally administered to male rats at 20, 40 or 120 mg/kg/day for 9 weeks. The rats were then euthanized, and serum, testis, epididymis, prostate gland, seminal vesicle, preputial gland, levator ani muscle and sphincter ani samples were collected. Sperm parameters were obtained by computer-assisted sperm analysis. Serum hormone levels were measured by ELISA. Protein expression levels were detected by immunohisto-chemistry. Apoptosis was assessed with the DeadEnd (TM) Colorimetric Apoptosis Detection System. The results indicated that the sperm average path velocity, straight line velocity and curvilinear velocity were significantly decreased in the 120 mg/kg cimetidine group compared with the control group, while luteinizing hormone and testosterone levels were significantly higher compared with the control group. Testicular lesions were observed by histopathology in the 120 mg/kg cimetidine group. The amounts of cells positive for cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-kappa B) were increased in the 120 mg/kg cimetidine group compared with the control group. The amounts of cells positive for iNOS were increased in all cimetidine treatment groups. In addition, apoptotic cells were significantly more abundant in the 120 mg/kg cimetidine group compared with the control group, as indicated by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling. Overall, 9 weeks of oral cimetidine induced pathological changes in the testicles and hormone secretion disorder in rats. COX-2, iNOS and NF-kappa B upregulation and induction of apoptosis may be associated with the reproductive toxicity caused by cimetidine.

http://dx.doi.org/10.3892%2Fetm.2018.6065

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McCoy E.R. et al. Altered DNA Methylation in the Developing Brains of Rats Genetically Prone to High versus Low Anxiety // J. Neurosci. 2019. Vol. 39, № 16. P. 3144–3158.

There is growing evidence of abnormal epigenetic processes playing a role in the neurobiology of psychiatric disorders, although the precise nature of these anomalies remains largely unknown. To study neurobiological (including epigenetic) factors that influence emotionality, we use rats bred for distinct behavioral responses to novelty. Rats bred for low novelty response (low responder [LR]) exhibit high levels of anxiety- and depressive-like behavior compared with high novelty responder (HR) rats. Prior work revealed distinct limbic brain development in HR versus LR rats, including altered expression of genes involved in DNA methylation. This led us to hypothesize that DNA methylation differences in the developing brain drive the disparate HR/LR neurobehavioral phenotypes. Here we report altered DNA methylation markers (altered DNA methyltransferase protein levels and increased global DNA methylation levels) in the early postnatal amygdala of LR versus HR male rats. Next-generation sequencing methylome profiling identified numerous differentially methylated regions across the genome in the early postnatal HR/LR amygdala. We also contrasted methylat ion profiles of male HRs and LRs with a control rat strain that displays an intermediate behavioral phenotype relative to the HR/LR extremes; this revealed that the LR amygdalar methylome was abnormal, with the HR profile more closely resembling that of the control group. Finally, through two methylation manipulations in early life, we found that decreasing DNA methylation in the developing male and female amygdala improves adult anxiety- and depression-like behavior. These findings suggest that inborn DNA methylation differences play important roles in shaping brain development and lifelong emotional behavior.

http://dx.doi.org/10.1523%2FJNEUROSCI.1157-15.2019

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Perkins A.E. et al. Analysis of c-Fos induction in response to social interaction in male and female Fisher 344 rats // Brain Res. 2017. Vol. 1672. P. 113–121.

Sex differences in the expression of social behavior are typically apparent in adolescent and adult rats. While the neurobiology underlying juvenile social play behavior has been well characterized, less is known about discrete brain regions involved in adult responsiveness to a same sex peer. Furthermore, whether adult males and females differ in their responsiveness to a social interaction in terms of neuronal activation indexed via immediate early gene (IEG) expression remains to be determined. Thus, the present study was designed to identify key sites relevant to the processing of sensory stimuli (generally) or social stimuli (specifically) after brief exposure to a same-sex social partner by assessing IEG expression. Four-month-old male and female Fisher (F) 344 rats (N = 38; n = 5-8/group) were either left undisturbed in their home cage as controls (HCC), exposed to a testing context alone for 30 min (CXT), or were placed in the context for 20 min and then allowed to socially interact (SI) with a sex-matched conspecific for 10 min. Females demonstrated greater levels of social behavior, relative to males. Analysis of c-Fos induction revealed that females exhibited greater c-Fos expression in the prefrontal cortex, regardless of condition. In many brain regions, induction was similar in the CXT and SI groups. However, in the bed nucleus of the stria terminalis (BNST), females exhibited greater c-Fos induction in response to the social interaction relative to their male counterparts, indicating a sex difference in responsivity to social stimuli. Taken together, these data suggest that the BNST is a sexually dimorphic region in terms of activation in response to social stimuli. (C) 2017 Elsevier B.V. All rights reserved.

http://dx.doi.org/10.1016%2Fj.brainres.2017.07.022

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Rahmouni F., Daoud S., Rebai T. Teucrium polium attenuates carbon tetrachloride-induced toxicity in the male reproductive system of rats // Andrologia. 2019. Vol. 51, № 2. P. e13182.

The aim of this study was to investigate the protective effects of Teucrium polium (T. polium) on carbon tetrachloride (CCl4)-induced male reproductive system damage. The effects of T. polium and vitamin C (Vit C) on sperm parameters, gonadotrophin and testosterone levels, oxidative status and testis tissue structure were assessed in CCl4-treated male rats. CCl4 caused significant alteration of sperm parameters in epididymal and testicular tissues, a decrease in hormone levels, and a decrease in antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in testicular tissues. A noteworthy increase in malondialdehyde (MDA) level was induced in CCl4-treated rats with some histopathological damages on the testes compared with control group. Remarkable ameliorations were observed with respect to all the previous parameters, following the administration of CCl4 with T. polium, and with vitamin C used as a positive control, when compared with CCl4 alone. Teucrium polium extracts showed good antioxidant performance, suggesting its protective effect against chemically induced reprotoxicity.

http://dx.doi.org/10.1111%2Fand.13182

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Randall P.A. et al. Effects of nicotine conditioning history on alcohol and methamphetamine self-administration in rats // Pharmacol. Biochem. Behav. 2019. Vol. 179. P. 1–8.

Background: Smoking constitutes a significant public health risk. Alcohol and methamphetamine use disorders are also highly co-morbid with smoking, further increasing negative health outcomes. An important question in determining the underlying neurobiology of nicotine poly-drug use is understanding whether having a positive history with nicotine effects alters later drug-taking behavior. Methods: The current experiments sought to elucidate whether having an appetitive nicotine conditioning history would affect later alcohol or methamphetamine self-administration. Adult male and female Long-Evans rats were first trained on a discriminated goal-tracking task in which the interoceptive effects of nicotine predicted sucrose reinforcement. As a control, pseudo-conditioned groups were included that had equated nicotine and sucrose experience. Rats were then shifted to either alcohol self-administration or methamphetamine self-administration. Results: Nicotine conditioning history had no effect on acquisition or maintenance of alcohol self-administration in males or females. In contrast, an appetitive nicotine conditioning history decreased methamphetamine self-administration in female rats, but not males. Conclusions: In female, but not male, rats, an appetitive conditioning history with nicotine decreases methamphetamine, but not alcohol, self-administration. This dissociation suggests that the effects may be due to a specific increase in the reinforcing value of methamphetamine. This may have implications for better understanding the progression of drug use from nicotine to methamphetamine.

http://dx.doi.org/10.1016%2Fj.pbb.2019.01.005

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Rehman H. et al. Toxicological effects of furan on the reproductive system of male rats: An “in vitro” and “in vivo”-based endocrinological and spermatogonial study // Chemosphere. 2019. Vol. 230. P. 327–336.

Furan is a colorless toxic chemical produced in various food items during heat processing and in chemical industries. Both in vitro and in vivo studies have reported that it induces oxidative stress and endocrine disruption; however, limited data are available regarding the effects of furan on the reproduction of mammals. In the present study, an in vitro experiment was designed to investigate the direct effects of furan exposure on oxidative stress and testosterone concentration in rat testicular tissue. Furan not only generated high oxidative stress but also decreased antioxidant enzyme activity in the testicular tissue. On the basis of in vitro study results, an in vivo sub-chronic exposure study was performed. Male rats were orally exposed to different concentrations of furan (0, 5, 10, 20, and 40 mg kg(-1)). An increase (P < 0.05) of reactive oxygen species (ROS) and of the lipid profile (cholesterol, triglycerides, and LDL) in higher dose treatment groups of furan was observed, while total protein content and antioxidant enzyme activity were considerably decreased after furan exposure. Also, plasma and intratesticular testosterone concentrations were reduced in high-dose treatment groups. Sperm parameters such as sperm viability, sperm count, and sperm motility showed a decrease (P < 0.05) in a dose-dependent manner. Histopathological findings revealed significant alterations in testis and epididymis tissues. These results confirm that furan can induce toxic effects on the reproductive system of male rats. (C) 2019 Elsevier Ltd. All rights reserved.

http://dx.doi.org/10.1016%2Fj.chemosphere.2019.05.063

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Russo C. et al. Effects of different musical frequencies on NPY and Ghrelin secretion in the rat hypothalamus // Brain Res. Bull. 2017. Vol. 132. P. 204–212.

It is known that exists a relationship between listening to music and food intake. Hypothalamus appears to integrate the orexigenic properties of a novel peptide, ghrelin (Ghre) that induces food intake through neuropeptide Y (NPY). Ghre stimulates appetite by acting on the ventral hypothalamus, which controls food intake. Ghre is secreted from the stomach and circulates in the bloodstream under fasting conditions, sending a hunger signal from the periphery to the Central Nervous System. The aim of this study was to evaluate, in the rat, the effects of different musical frequencies (432 and 440 Hz) on the Ghre and NPY expression in the hypothalamic neurons through immunohistochemistry; in addition, we investigated on the different production of Ghre in the serum through Western blot assay (Wb), in relation to the body weight of animals. Ghre-immunopositive cells were counted, showing a significant increase in music-treated compared to the control (CTR) group. Similarly, music-treated rats showed increased levels of Ghre in the serum compared to CTR animals. Finally, the body weight of animals was affected by music. In particular, music exposure was able to stimulate the body weight increase and, interestingly, the increase was higher when animals were exposed to music at 440 Hz. Together, the results strongly support the hypothesis that different musical frequencies could affect food intake by modulating the hypothalamic Ghre expression and its release.

http://dx.doi.org/10.1016%2Fj.brainresbull.2017.06.002

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Sansevero G. et al. Intranasal BDNF administration promotes visual function recovery in adult amblyopic rats // Neuropharmacology. 2019. Vol. 145. P. 114–122.

Amblyopia is the most common cause of visual impairment in one eye, with a prevalence of 1-5% in the world population. While amblyopia can be efficiently treated in children, it becomes irreversible in adults, due to the decline in neural plasticity past the end of the visual cortex critical period. Accordingly, no pharmacological approaches are available to rescue visual functions in adult amblyopic subjects. We report that non-invasive intranasal infusion of BDNF increased levels of this neurotrophic factor in V1 and induced a recovery of visual acuity, ocular dominance and visual depth perception in adult amblyopic rats, both in reverse-occluded animals and in those with unrestricted binocular sight. Visual recovery was long-lasting, and was prevented by pharmacological blockade of TrkB signaling in the visual cortex. These results underscore the possibility to replace invasive BDNF central administration with a safe procedure of potential interest in a number of currently still cureless central nervous system pathologies. This article is part of the Special Issue entitled "Neurobiology of Environmental Enrichment". (C) 2018 Elsevier Ltd. All rights reserved.

http://dx.doi.org/10.1016%2Fj.neuropharm.2018.02.006

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Santiago A.N. et al. Early life trauma increases threat response of peri-weaning rats, reduction of axo-somatic synapses formed by parvalbumin cells and perineuronal net in the basolateral nucleus of amygdala // J. Comp. Neurol. 2018. Vol. 526, № 16. P. 2647–2664.

Early life trauma is a risk factor for life-long disorders related to emotional processing, but knowledge underlying its enduring effect is incomplete. This study was motivated by the hypothesis that early life trauma increases amygdala-dependent threat responses via reduction in inhibition by parvalbumin (PV) interneurons and perineuronal nets (PNN) supporting PV cells, thus increasing excitability of the basolateral amygdala (BLA). From postnatal day (PN) 8-12, rat pups of both sexes were reared under normal bedding or under insufficient nest-building materials to induce maternal-to-infant maltreatment trauma (Scarcity-Adversity Model, SAM). At weaning age of PN23, the SAM group exhibited increased threat responses to predator odor. The SAM-induced increase in threat response was recapitulated in normally reared PN22-23 rats that were unilaterally depleted of PNN in the BLA by the enzymes, chondroitinase-ABC plus hyaluronidase at PN19-20. Light and electron microscopic analysis of the BLA revealed that anterior-to-mid levels of SAM group's BLAs exhibited decreased PNN intensity and decreased axo-somatic synapses between PV-to-principal pyramidal-like neurons and PV-to-PV. PV and PNN densities (cells/mm(2)) in the BLA of both control (CON) and SAM groups were still low at PN12 and SAM delayed the ontogenetic rise of PV intensity and PNN density. Moreover, PV cell density in the anterior-to-mid BLA correlated negatively with threat response of CON animals, but not for SAM animals. Thus, reduction of PNN-supported, PV-mediated somatic inhibition of pyramidal cells provides a mechanistic support for the enduring effect of early life maltreatment manifested as increasing innate threat response at weaning.

http://dx.doi.org/10.1002%2Fcne.24522

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Sedaghat K. et al. Mesolimbic dopamine system and its modulation by vitamin D in a chronic mild stress model of depression in the rat // Behav. Brain Res. 2019. Vol. 356. P. 156–169.

Depression, a common mood disorder, involves anhedonia and defects in reward circuits and mesolimbic dopamine transmission in the striatum and nucleus accumbens (NAc). Active vitamin-D, (1,25-(OH) 2 vitamin-D3), exerts protective and regulatory effects on the brain dopamine system. In this study, key depression-like symptoms were induced in rats by chronic mild-stress (CMS) and the comparative effect of treatment with 1,25(OH) 2 vitamin-D3 (5, 10 mu g/kg, or vehicle; i.p., twice weekly) or fluoxetine (5 mg/kg or vehicle, i.p., daily) on anhedonic behavior, locomotor activity and anxiety-like behavior was examined using sucrose preference test (SPT), open field test (OFT) and novel object exploration test (NOT), respectively. We also measured serum corticosterone levels and dopamine transporter-immunoreactivity (DAT-ir) levels in NAc shell and core. CMS exposure for 3 weeks was followed by a SPT and thereafter CMS was continued for 5 weeks, along with vitamin-D or fluoxetine treatment and further testing, which was concluded with another SPT. Vitamin-D treatment enhanced sucrose preference (P < 0.01; an hedonic effect) and increased object exploration (P < 0.01) in CMS rats. CMS significantly reduced the level of DAT-ir in NAc (P < 0.0001). Vitamin-D treatment restored/increased DAT-ir levels (P < 0.0001) in CMS rat NAc (core/ shell), compared to levels in fluoxetine treated and non-treated CMS rats. Vitamin-D did not alter locomotor activity or produce an anxiolytic effect in the OFT. These data suggest that similar to the antidepressant, fluoxetine, regular vitamin-D treatment can improve 'anhedonia-like symptoms' in rats subjected to CMS, probably by regulating the effect of dopamine-related actions in the NAc.

http://dx.doi.org/10.1016%2Fj.bbr.2018.08.020

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Sharma P., Khan I.A., Singh R. Curcumin and Quercetin Ameliorated Cypermethrin and Deltamethrin-Induced Reproductive System Impairment in Male Wistar Rats by Upregulating The Activity of Pituitary-Gonadal Hormones and Steroidogenic Enzymes // Int. J. Fertil. Steril. 2018. Vol. 12, № 1. P. 72–80.

Background: Dietary antioxidants protect tissues and organs against insecticides/xenobiotic-induced damage. In the present study, we evaluated the results of exposure to synthetic pyrethroid insecticides, cypermethrin (Cyp) and deltamethrin (Del) and possible protective effects of curcumin and quercetin on reproductive system in male Wistar rats. Materials and Methods: In this controlled experimental study, 42 male Wistar rats were randomly divided into 7 groups of 6 animals. Group A served as control, group B was exposed to Cyp (2 mg/kg.bw), group C was exposed to Del (2 mg/kg.bw), group D was exposed to Cyp+Del (2 mg/kg.bw each), group E was exposed to Cyp+Del and treated with curcumin (100 mg/kg.bw), group F was exposed to Cyp+Del and treated with quercetin (100 mg/kg.bw) and group G was exposed to Cyp+Del and treated with quercetin+curcumin for 45 days. Results: Exposure to Cyp and Del caused decreases in reproductive organs weight, sperm count, sperm motility, level of sex hormones viz. testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH), steroidogenic enzymes viz. 3 beta-hydroxyl steroid dehydrogenase (3 beta-HSD) and 17 beta-HSD, non-enzymatic antioxidant glutathione (GSH) and enzymatic antioxidants viz. superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) activity and increases in sperm abnormalities and lipid peroxidation (LPO). The exposure also adversely affected the histo-achitecture of testes. Single and combined treatment with curcumin and quercetin significantly ameliorated Cyp and Del-induced damage in reproductive system. Conclusion: Curcumin and quercetin protected against Cyp and Del-induced reproductive system toxicity and oxidative damage in rats. The increases in activities of 3 beta-HSD and 17 beta-HSD with concomitant increases in testosterone were mainly responsible for ameliorating effects of curcumin and quercetin. Curcumin showed slightly better activity as compared to quercetin. The combination of both antioxidants offered more protection compared to each one alone.

http://dx.doi.org/10.22074%2Fijfs.2018.5160

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Shortall S.E. et al. Characterization of Behavioral, Signaling and Cytokine Alterations in a Rat Neurodevelopmental Model for Schizophrenia, and Their Reversal by the 5-HT6 Receptor Antagonist SB-399885 // Mol. Neurobiol. 2018. Vol. 55, № 9. P. 7413–7430.

Post-weaning social isolation of rats produces neuroanatomical, neurochemical and behavioral alterations resembling some core features of schizophrenia. This study examined the ability of the 5-HT6 receptor antagonist SB-399885 to reverse isolation-induced cognitive deficits, then investigated alterations in hippocampal cell proliferation and hippocampal and frontal cortical expression of selected intracellular signaling molecules and cytokines. Male Lister hooded rats (weaned on post-natal days 21-24 and housed individually or in groups of 3-4) received six i.p. injections of vehicle (1% Tween 80,1 mL/kg) or SB-399885 (5 or 10 mg/kg) over a 2-week period starting 40 days post-weaning, on the days that locomotor activity, novel object discrimination (NOD), pre-pulse inhibition of acoustic startle and acquisition, retention and extinction of a conditioned freezing response (CFR) were assessed. Tissue was collected 24 h after the final injection for immunohistochemistry, reverse-phase protein microarray and western blotting. Isolation rearing impaired NOD and cue-mediated CFR, decreased cell proliferation within the dentate gyrus, and elevated hippocampal TNF alpha levels and Cdc42 expression. SB-399885 reversed the NOD deficit and partially normalized CFR and cell proliferation. These effects were accompanied by altered expression of several members of the c-Jun N-terminal Kinase (JNK) and p38 MAPK signaling pathways (including TAK1, MKK4 and STAT3). Although JNK and p38 themselves were unaltered at this time point hippocampal TAK1 expression and phosphorylation correlated with visual recognition memory in the NOD task. Continued use of this neurodevelopmental model could firther elucidate the neurobiology of schizophrenia and aid assessment of novel therapies for drug-resistant cognitive symptoms.

http://dx.doi.org/10.1007%2Fs12035-018-0940-0

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Souza R.R. et al. The M-Maze task: An automated method for studying fear memory in rats exposed to protracted aversive conditioning // J. Neurosci. Methods. 2018. Vol. 298. P. 54–65.

Background: Fear conditioning (FC) in rodents is the most used animal model to investigate the neurobiology of posttraumatic stress disorder (PTSD). Although research using FC has generated a better understanding of fear memories, studies often rely on mild or moderate FC training and behavioral analysis generally focuses on measuring freezing responses within few test sessions. New method: We introduce the M-Maze task, a system that measures extinction of conditioned fear using suppression of operant behavior. The apparatus consists of an M-shaped maze where rats are trained to alternate nose poking at two pellet dispensers. Proximity sensors measure the animal's locomotion, as well as the latencies and number of operant behaviors. Here we also describe the protracted aversive conditioning (PAC), a rat model of severe fear that induces resistant extinction following a 4-day conditioning protocol that combines delay, unpredictable, and short- and long-trace conditioning. Results: An intense one-day auditory FC protocol induced a sharp elevation in transit time and suppression of nose pokes by conditioned cues, but in contrast to what is found in PTSD patients, fear extinction was rapidly observed. On the other hand, PAC alone or in combination with exposure to single prolonged stress induced persistent extinction impairments in M-Maze tests, as well as enhanced anxiety, and social withdrawal. Comparison with other existing methods: The M-Maze task is fully automated and allows multiple animals to be tested simultaneously in long-term experiments. Moreover, PAC training can be an alternative approach to study extinction-resistant fear. Conclusions: The M-Maze task allows rapid and unbiased measurements of fear-induced suppression. We suggest that long-term assessment of extinction impairments would lead to a better understanding of the neurobiology of persistent fear and the screening for new therapies. Published by Elsevier B.V.

http://dx.doi.org/10.1016%2Fj.jneumeth.2018.02.004

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Uchewa O.O., Ezugworie O.J. Countering the effects of lead as an environmental toxicant on the microanatomy of female reproductive system of adult wistar rats using aqueous extract of Ficus vogelii // J. Trace Elem. Med. Biol. 2019. Vol. 52. P. 192–198.

Background: Lead without nutritional value is a widely studied occupational and environmental toxicant. Leads' toxic effects on female reproduction are decreased fertility, inability to sustain pregnancy and reduced pregnancy. Objective: This study aimed at examining the effect of oral administration of lead acetate (1.5 mg/kg) on the histology of female albino Wistar rats' ovary and Uterus and the extracts' protective role against toxicity. Methods: The experiment took 28 days involving 25 female Wistar rats divided into 5 groups A, B, C, D and E. A is an untreated group that received normal saline, D lead acetate group that received lead acetate solution, E received aqueous extract, B and C low and high dose of aqueous extract respectively and lead acetate solution. Results: The positive control group showed a significant increase in SOD at P <= 0.01 compared to the negative control. Group E showed significant decrease ovarian SOD. The organs weights were significantly reduced in group D. The changes seen in the organs include oedema, necrosis, optical empty spaces, denudations and fatty changes. Administrating the extract protected the organs against the lead acetate. These alterations are shown to cause infertility in female rats. Conclusion: The results suggested that the extract has protective role against lead reproductive toxicity.

http://dx.doi.org/10.1016%2Fj.jtemb.2018.12.016

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Vazquez-Leon P. et al. Differential effects of cholecystokinin (CCK-8) microinjection into the ventrolateral and dorsolateral periaqueductal gray on anxiety models in Wistar rats // Horm. Behav. 2018. Vol. 106. P. 105–111.

Cholecystokinin (CCK) is one of the main neurohormone peptide systems in the brain, and a major anxiogenic mediator. The periaqueductal gray (PAG) is a key midbrain structure for defensive behaviors, which could include anxiety, fear, or even panic. The CCK system has wide distribution in the PAG, where the dorsolateral region (DL) participates in active defensive behavior and the ventrolateral region (VL) in passive defensive behavior. The aim of this study was to assess the effect of CCK-8 microinjection into DL-PAG or VL-PAG on anxiety-like behavior through two tests: elevated plus maze (EPM) and defensive burying behavior (DBB). CCK-8 (0.5 and 1.0 mu g/0.5 mu L) presently microinjected into the DL-PAG produced an anxiogenic-like effect on the EPM evidenced by decreasing the time spent/number of entries in open arms compared to vehicle group. Additionally, the latency to burying decreased and burying time increased on the DBB test. Contrarily, CCK-8 microinjected into the VL-PAG resulted in greater open-arm time and more open-arm entries compared to the vehicle-microinjected group. The results on the DBB test confirmed an anxiolytic-like response of CCK-8 into the VL-PAG. In conclusion, CCK-8 microinjected into DL-PAG produced anxiety-like behavior on EPM, and for first time reported on DBB. Contrarily, CCK-8 microinjected into the VL-PAG reduced anxiety-like behavior also for first time reported using both behavioral models EPM and DBB.

http://dx.doi.org/10.1016%2Fj.yhbeh.2018.10.003

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Venkataraman S.S., Joseph M., Dafny N. Concomitant behavioral and prefrontal cortex neuronal responses following acute and chronic methylphenidate exposure in adolescent and adult rats // Brain Res. Bull. 2019. Vol. 144. P. 200–212.

There is growing concern that the psychostimulant Methylphenidate (MPD) is being abused for cognitive enhancement and recreation by healthy adults and adolescents seeking to improve their work or academic performance. This study concomitantly recorded the behavioral and prefrontal cortex (PFC) neuronal activity in freely behaving animals exposed to acute and chronic MPD doses (0.6, 2.5, and 10.0 mg/kg MPD) in order to compare MPD effects on adult and adolescent rats. The PFC is one of the primary brain areas affected by MPD and the drug of choice for treating ADHD. Moreover, the PFC is one of the last brain areas to complete development, suggesting that the behavioral and neurophysiological response to MPD may differ in adolescents and adults. In both adult and adolescent animals, it was observed that the same repetitive (chronic) dose of either 0.6, 2.5, or 10.0 mg/kg MPD elicited behavioral sensitization in some animals and tolerance in others, experimental biomarkers indicating drug of abuse symptoms, and the majority of PFC units recorded in animals expressing behavioral sensitization or tolerance to chronic MPD exposure responded by increasing and decreasing their neuronal firing rate, respectively. Further, it was shown that high doses of 10.0 mg/kg MPD significantly modified adolescent behavioral activity but did not impact adults suggesting that adolescents may be more receptive to chronic MPD exposure. These findings raise concerns regarding the use and abuse of MPD in normal, healthy individuals and support the notion that the adolescent PFC is more susceptible than the adult PFC to neuromodulation from chronic MPD use.

http://dx.doi.org/10.1016%2Fj.brainresbull.2018.11.004

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Wang Y. et al. High-concentration sevoflurane exposure in mid-gestation induces apoptosis of neural stem cells in rat offspring // Neural Regen. Res. 2018. Vol. 13, № 9. P. 1575–1584.

Sevoflurane is the most commonly used volatile anesthetic during pregnancy. The viability of neural stem cells directly affects the development of the brain. However, it is unknown whether the use of sevoflurane during the second trimester affects the survival of fetal neural stem cells. Therefore, in this study, we investigated whether exposure to sevoflurane in mid-gestation induces apoptosis of neural stem cells and behavioral abnormalities. On gestational day 14, pregnant rats were anesthetized with 2% or 3.5% sevoflurane for 2 hours. The offspring were weaned at 28 days and subjected to the Morris water maze test. The brains were harvested to examine neural stem cell apoptosis by immunofluorescence and to measure Nestin and SOX-2 levels by western blot assay at 6, 24 and 48 hours after anesthesia as well as on postnatal day P0, 14 and P28. Vascular endothelial growth factor (VEGF) and phosphoinositide 3-kinase (PI3K)/AKT pathway protein levels in fetal brain at 6 hours after anesthesia were assessed by western blot assay. Exposure to high-concentration (3.5%) sevoflurane during mid-gestation increased escape latency and path length to the platform, and it reduced the average duration spent in the target quadrant and platform crossing times. At 6, 24 and 48 hours after anesthesia and at P0, P14 and P28, the percentage of Nestin/terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells was increased, but Nestin and SOX-2 protein levels were decreased in the hippocampus of the offspring. At 6 hours after anesthesia, VEGF, PI3K and phospho-AKT (p-AKT) levels were decreased in the fetal brain. These changes were not observed in animals given low-concentration (2%) sevoflurane exposure. Together, our findings indicate that exposure to a high concentration of sevoflurane (3.5%) in mid-gestation decreases VEGF, PI3K and p-AKT protein levels and induces neural stem cell apoptosis, thereby causing learning and memory dysfunction in the offspring.

http://dx.doi.org/10.4103%2F1673-5374.237121

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Weber R.A. et al. Regionally Specific Effects of Oxytocin on Reinstatement of Cocaine Seeking in Male and Female Rats // Int. J. Neuropsychopharmacol. 2018. Vol. 21, № 7. P. 677–686.

Background: Oxytocin reduces cued reinstatement of cocaine seeking in male and female rats, but the underlying neurobiology has not been uncovered. The majority of effort on this task has focused on oxytocin and dopamine interactions in the nucleus accumbens core. The nucleus accumbens core is a key neural substrate in relapse, and oxytocin administration in the nucleus accumbens core reduces reinstatement to methamphetamine cues. Further, the nucleus accumbens core has strong glutamatergic innervation from numerous regions including the prefrontal cortex. Thus, we hypothesize that oxytocin regulates presynaptic glutamate terminals in the nucleus accumbens core, thereby affecting reinstatement. Methods: To begin to evaluate this hypothesis, we examined the effects of intra-nucleus accumbens core oxytocin on extracellular glutamate levels in this region. We next determined if direct infusion of oxytocin into the nucleus accumbens core could attenuate cued reinstatement of cocaine seeking in a manner dependent on metabotropic glutamate 2/3 receptors. Finally, we tested if site-specific application of oxytocin in the prefrontal cortex reduced cued reinstatement of cocaine seeking. Results: We found an increase in nucleus accumbens core extracellular glutamate for several minutes following reverse dialysis of oxytocin. In male and female rats with a history of cocaine self-administration, site-specific application of oxytocin in the nucleus accumbens core and prefrontal cortex had opposing effects, decreasing and increasing cued reinstatement, respectively. The mGlu2/3 antagonist LY-341495 reversed oxytocin's ability to attenuate cued reinstatement. Conclusions: While the precise mechanism by which oxytocin increases nucleus accumbens core glutamate is yet to be determined, the present results clearly support oxytocin mediation of glutamate neurotransmission in the nucleus accumbens core that impacts cued cocaine seeking.

http://dx.doi.org/10.1093%2Fijnp%2Fpyy025

38. PDF
Wu W.-L. et al. The Effect of ASIC3 Knockout on Corticostriatal Circuit and Mouse Self-grooming Behavior // Front. Cell. Neurosci. 2019. Vol. 13. P. 86.

Stereotypic and/or repetitive behavior is one of the major symptoms of autism spectrum disorder (ASD). Increase of self-grooming behavior is a behavioral phenotype commonly observed in the mouse models for ASD. Previously, we have shown that knockout of acid-sensing ion channel 3 (ASIC3) led to the increased self-grooming behavior in resident-intruder test. Given the facts that ASIC3 is mainly expressed in the peripheral dorsal root ganglion (DRG) and conditional knockout of ASIC3 in the proprioceptors induced proprioception deficits. We speculate a hypothesis that stereotypic phenotype related to ASD, pararalled with striatal dysfunction, might be caused by proprioception defect in the peripheral sensory neuron origin. Herein, we investigate in depth whether and how ASIC3 is involved in the regulation of self-grooming behavior. First, we observed that Asic3 null mutant mice exhibited increased self-grooming in social interaction during juvenile stage. Similarly, they displayed increased self-grooming behavior in a novel cage in the absence of cagemate. To further understand the mechanism by which ASIC3 affects grooming behavior, we analyzed neurochemical, neuropathological and electrophysiological features in the dorsal striatum of Asic3 null mutant mice. Knockout of Asic3 increased dopamine (DA) activity and phospho-ERK immunoreactivities in the dorsal striatum. Furthermore, we detected a lower paired-pulse ratio (PPR) and impaired long-term potentiation (LTP) in corticostriatal circuits in Asic3 null mutant mice as compared with wild-type (WT) littermates. Moreover, knockout of Asic3 altered the medial spiny neurons in the striatum with defects in presynaptic function and decrease of dendritic spines. Lastly, genetic ablation of Asic3 specifically in parvalbumin-positive (PV+) cells resulted in the increase of self-grooming behavior in mice. These findings suggest knockout of Asic3 in the PV+ neurons alters grooming behavior by co-opting corticostriatal circuits.

http://dx.doi.org/10.3389%2Ffncel.2019.00086

39. PDF
Yoshino Y. et al. Endothelial nitric oxide synthase in rat brain is downregulated by sub-chronic antidepressant treatment // Psychopharmacology. 2017. Vol. 234, № 11. P. 1663–1669.

Background Nitric oxide (NO) is a neurotransmitter that may be related to major depressive disorder (MDD) because the selective neuronal NO synthase (NOS) inhibitor, 7-nitroindazole, induces a dose-dependent antidepressant-like effect. NO modulates major neurotransmitters involved in the neurobiology of MDD, such as norepinephrine, serotonin, dopamine, and glutamate. In this study, we investigated the effects of antidepressants as NO modulators in acute and sub-chronic treatments. Methods Rats were injected with the SSRI paroxetine (PAR, 10 mg/kg), the SNRI milnacipran (MIL, 30 mg/kg), or the NaSSA mirtazapine (MIR, 10 mg/kg) for acute (1 h) or sub-chronic (3 weeks) treatment prior to analysis of nine brain regions (frontal cortex, temporal cortex, striatum, thalamus, hippocampus, midbrain, pons, cerebellum, and olfactory bulb). The mRNA expression levels of three NOS subtypes (neuronal: nNOS, inducible: iNOS, and endothelial: eNOS) were analyzed using real-time PCR with Taqman probes. Results Acute MIR treatment significantly increased nNOS mRNA expression in the hippocampus, midbrain, cerebellum and olfactory bulb, and iNOS mRNA expression in the frontal cortex and midbrain. Acute PAR and MIR treatments significantly increased eNOS mRNA expression in most brain regions. Conversely, sub-chronic treatment with all types of antidepressants resulted in significant decreases of eNOS mRNA expression in most brain regions. Conclusions Sub-chronic treatment with the three types of antidepressants consistently decreased eNOS mRNA expression levels in the rat brain. These effects may be associated with the involvement of the NO system in the mechanism of action of antidepressants.

http://dx.doi.org/10.1007%2Fs00213-017-4567-z

40. PDF
Zhang C., Kalueff A.V., Song C. Minocycline ameliorates anxiety-related self-grooming behaviors and alters hippocampal neuroinflammation, GABA and serum cholesterol levels in female Sprague-Dawley rats subjected to chronic unpredictable mild stress // Behav. Brain Res. 2019. Vol. 363. P. 109–117.

Neuroinflammation induced by stress results in aberrant neurotransmission and dyslipidemia, which can trigger depression- and anxiety-like behaviors. Gamma-aminobutyric acid (GABA) and cholesterol play a crucial role in anxiety-like states, including self-grooming - a common stress-evoked rodent behavior. However, the interaction between neuroinflammation, GABA and cholesterol under stress, and their effects on grooming, remain unclear. Here, we utilize the chronic unpredictable mild stress (CUMS) rat cohort used previously in our Zhang et al. (2019) study, to examine whether CUMS affects grooming behavior, and whether minocycline, a microglia antagonist, can correct these behavioral deficits, accompanied by altering hippocampal neuroinflammation, GABA and serum cholesterol levels. Female Sprague-Dawley rats underwent a 6-week CUMS and received daily minocycline (40 mg/kg, i.p.) during this period, followed by behavioral testing in the open field test. Serum cholesterol, inflammatory cytokines and GABA levels in hippocampus were assayed by ELISA. CUMS significantly decreased locomotion, rearing, central zone entries and time spent in the open field center compared to unstressed controls. CUMS also strongly affected self-grooming behaviors, increasing the frequency of grooming episodes, the number of transitions, interruptions and individual elements of various grooming phases. However, these CUMS-induced behavioral abnormalities were corrected by minocycline. Likewise, CUMS elevated total serum cholesterol and lowered serum high-density lipoprotein cholesterol, whereas minocycline ameliorated these responses. CUMS also lowered hippocampal GABA, whereas minocycline normalized CUMS-induced GABA in the hippocampus. We also found significant correlations between neuroinflammation and GABA, neuroinflammation and cholesterol, GABA and grooming, as well as cholesterol and grooming measures, further implicating stress-evoked neuroinflammation, GABA and cholesterol in the regulation of complex rodent behaviors. In summary, minocycline ameliorated CUMS-induced aberrant self-grooming behaviors in rats by altering hippocampal neuroinflammation, GABA and serum cholesterol levels.

http://dx.doi.org/10.1016%2Fj.bbr.2019.01.045

41. PDF
Zhang J. et al. iTRAQ-Based Protein Profiling in CUMS Rats Provides Insights into Hippocampal Ribosome Lesion and Ras Protein Changes Underlying Synaptic Plasticity in Depression // Neural. Plast. 2019. P. 7492306.

Hippocampal atrophy is one of the key changes in the brain implicated in the biology of depression. However, the precise molecular mechanism remains poorly understood due to a lack of biomarkers. In this research, we used behavioral experiments to evaluate anxiety and anhedonia levels in depressed rats using chronic unpredictable mild stress (CUMS) modeling. We also used isobaric tag for relative and absolute quantitation (iTRAQ) to identify the differentially expressed hippocampal proteins between depressed and normal rats. Bioinformatics analyses were also performed for a better understanding. The results showed that CUMS rats had higher anxiety and anhedonia levels than control rats, along with hippocampal lesions. Through iTRAQ and bioinformatics analyses, we found that ribosome proteins were significantly downregulated and Ras proteins exhibited a mixed change in the hippocampus of depressed rats. These findings suggest that the expression of hippocampal ribosome lesions and Ras proteins is significantly different in depressed rats than in control rats, providing new insights into the neurobiology of depression.

http://dx.doi.org/10.1155%2F2019%2F7492306

42. 040578
Алекперов С.И., Суетов А.А., Лаврененок Л.В., Ефремов В.И., Кимстач А.Н. ВЛИЯНИЕ ПЕРЕМЕННОГО МАГНИТНОГО ПОЛЯ КРАЙНЕ НИЗКОЙ ЧАСТОТЫ НА РЕПРОДУКТИВНУЮ СИСТЕМУ САМОК КРЫС ПРИ ОБЛУЧЕНИИ В ПЕРИОДЫ ЭМБРИОНАЛЬНОГО И ПОСТНАТАЛЬНОГО РАЗВИТИЯ // Проблемы репродукции. 2018. Т. 24. № 5. С. 11-19.

Цель исследования — изучить изменения репродуктивной системы самок крыс, подвергавшихся воздействию переменного магнитного поля крайне низкой частоты (ПеМП КНЧ) в периоды эмбрионального и постнатального развития. Материал и методы. Воздействию ПеМП КНЧ с частотой 8 Гц в течение 9 нед, включавших периоды спаривания, гестации и грудного вскармливания, подвергали 90 самок крыс линии Wistar, которых распределили на три группы по 30 крыс: 1-я группа — применяли напряженность поля 4 кА/м; 2-я группа — напряженность поля 6,5 кА/м; 3-я группа — имитационный контроль. У крыс-самок в полученном потомстве, которое вместе с матерями продолжали облучать до суммарного срока воздействия 9 нед, исследовали продолжительность эстрального цикла, фертильность самок, качественные и количественные характеристики помета, уровень лютеинизирующего гормона, фолликулостимулирующего гормона, прогестерона и эстрадиола Ев сыворотке крови; морфологические изменения в яичниках и матке. Результаты. У подопытных крыс, подвергавшихся воздействию ПеМП КНЧ 8 Гц в течение эмбрионального и постнатального развития, не выявлено изменений продолжительности эстрального цикла, фертильности, изменений в количестве и массе живых крысят в помете, уровнях лютеинизирующего и фолликулостимулирующего гормонов в сыворотке крови, но отмечено снижение уровня прогестерона после воздействия ПеМП КНЧ с напряженностью поля 4 кА/м (p<0,05) и эстрадиола Епосле воздействия ПеМП КНЧ с напряженностью поля 6,5 кА/м (p<0,05)...

https://elibrary.ru/item.asp?id=36533462

43. 000231
Артамонов А.А., Боголюбов С.В., Елисеева Т.И., Поздняков О.Б., Елисеева И.В. ВЛИЯНИЕ ОЖИРЕНИЯ НА РЕПРОДУКТИВНУЮ СИСТЕМУ КРЫС / / Морфология. 2016. Т. 149. № 3. С. 19-19a.

https://elibrary.ru/item.asp?id=26565391

44. 005644
Верещако Г.Г., Чешик И.А., Чуешова Н.В., Шалатонин В.И., Горох Г.А., Бакшаева М.А., Цуканова Е.В., Козлов А.Е. ЭФФЕКТЫ СОЧЕТАННОГО ДЕЙСТВИЯ МАГНИТНОГО ПОЛЯ ПРОМЫШЛЕННОЙ ЧАСТОТЫ (50 ГЦ) И ОБЛУЧЕНИЯ В ДОЗЕ 1.0 ГР В КРОВИ И РЕПРОДУКТИВНОЙ СИСТЕМЕ КРЫС-САМЦОВ // Радиационная биология. Радиоэкология. 2018. Т. 58. № 6. С. 624-632.

Изучали влияние длительной экспозиции в магнитном поле промышленной частоты (МП ПЧ 50 Гц, 4 ч/день, 5 дней в неделю, 26 дней), внешнего ?-облучения в дозе 1.0 Гр и их сочетанного воздействия на некоторые показатели крови и репродуктивной системы крыс-самцов линии Вистар. Установлено, что действие экспериментальных факторов приводит к значительной лейкопении, падению числа моноцитов и гранулоцитов, более выраженным в начальном периоде (3-и сут). Реакция репродуктивной системы крыс-самцов на действующие факторы заключается в ускорении начальных этапов сперматогенеза и повышении количества круглых сперматид, однако число сперматид последующих стадий трансформации существенно снижается. Влияние МП ПЧ (50 Гц) и внешнего облучения в дозе 1.0 Гр (изолированно и сочетанно) на эпидидимальные сперматозоиды выражается в значительном падении их количества и жизнеспособности, гибели части клеток путем апоптоза и некроза, изменении активности глицеральдегид-3-фосфатдегидрогеназы и акрозина. В большинстве случаев выявлено синергическое взаимодействие длительного воздействия МП ПЧ (50 Гц) и внешнего облучения в дозе 1.0 Гр, которые вызывают выраженные нарушения в сперматозоидах. Существенное ухудшение их свойств при действии исследуемых экстремальных факторов, очевидно, негативно отразится на фертильности животных, особенно значительно при сочетанном воздействии.

https://elibrary.ru/item.asp?id=36564258

45. 005644
Верещако Г.Г., Чуешова Н.В. РЕАКЦИЯ ОРГАНОВ РЕПРОДУКТИВНОЙ СИСТЕМЫ И ЭПИДИДИМАЛЬНЫХ СПЕРМАТОЗОИДОВ КРЫС НА ЭЛЕКТРОМАГНИТНОЕ ИЗЛУЧЕНИЕ ОТ МОБИЛЬНОГО ТЕЛЕФОНА (1745 МГЦ) РАЗЛИЧНОЙ ПРОДОЛЖИТЕЛЬНОСТИ // Радиационная биология. Радиоэкология. 2017. Т. 57. № 1. С. 71-76.

Изучали изменение массы органов репродуктивной системы, количественных и качественных показателей эпидидимальных сперматозоидов крыс на 1-е и 30-е сут после прекращения электромагнитной экспозиции от мобильного телефона (1745 МГц, 8 ч/день, ППЭ 0.2-20 мкВт/см2) различной продолжительности (от 1 до 90 сут). Установлено, что на 1-е сут после электромагнитной экспозиции в течение 7 дней выявляется статистически значимое повышение абсолютной и относительной массы эпидидимисов и семенных пузырьков и числа эпидидимальных сперматозоидов. Увеличение продолжительности облучения до 14 дней сопровождается снижением вышеуказанных показателей, а при более продолжительном воздействии (30, 60 дней) абсолютная масса семенников возрастает; во всех остальных случаях значимых отклонений в массовых показателях органов репродуктивной системы не наблюдается. Экспозиция при 1745 МГц различной продолжительности, за исключением 7-дневного облучения, не оказывало существенного влияния на количество эпидидимальных сперматозоидов и фрагментацию ДНК в них, однако жизнеспособность зрелых половых клеток облученных животных независимо от продолжительности воздействия снижается...

https://elibrary.ru/item.asp?id=28919467

46. 040578
Верещако Г.Г., Чуешова Н.В., Цуканова Е.В., Бакшаева М.А. ВЛИЯНИЕ АЦЕТИЛ-L-КАРНИТИНА НА РЕПРОДУКТИВНУЮ СИСТЕМУ КРЫС-САМЦОВ WISTAR, ПОДВЕРГНУТЫХ ЭЛЕКТРОМАГНИТНОМУ ВОЗДЕЙСТВИЮ ОТ МОБИЛЬНОГО ТЕЛЕФОНА // Проблемы репродукции. 2017. Т. 23. № 5. С. 95-101.

Цель исследования — изучить влияние ацетил-L-карнитина (7 мг/кг) на репродуктивную систему крыс-самцов Wistar в 1-е и на 30-е сутки после экспозиции от мобильного телефона (1745 МГц, 8 ч в день, 30 дней). Материал и методы. Опыты проводили на крысах-самцах Wistar, которые были разделены на три группы: 1-я — интактный контроль; 2-я — животные, подвергнутые электромагнитной экспозиции от мобильного телефона (1745 МГц, ППЭ 0,2—20 мкВт/см, x? = 7,5±0,34 мкВт/см, 8 ч в день, 30 дней); 3-я — крысы, подвергнутые электромагнитному воздействию от мобильного телефона и получавшие ацетил-L-карнитин (7 мг/кг, через день, 30 дней). После декапитации у животных выделяли семенники, эпидидимисы и семенные пузырьки, массу которых оценивали. В суспензии ткани семенника методом проточной цитометрии (Cytomics FC 500, «Beckman Coulter», США) анализировали количественный состав популяции сперматогенных клеток по содержанию ДНК, в том числе: сперматогонии (2С), сперматоциты в S-фазе, сперматоциты I порядка (4С), круглые (1С), удлиненные (НС1) и продолговатые сперматиды (НС2)...

https://elibrary.ru/item.asp?id=30058305

47. 041871
Волошина И.С. ПОСЛЕДСТВИЯ ВЛИЯНИЯ ПАРОВ ТОЛУОЛА НА РЕПРОДУКТИВНУЮ СИСТЕМУ КРЫС-САМЦОВ //Тихоокеанский медицинский журнал. 2017. № 3 (69). С. 54-57.

В эксперименте изучалось микроскопическое строение внутренних органов половой системы половозрелых крыс-самцов, которые подвергались ингаляционному воздействию толуола. Данные, полученные в ходе исследования, позволяют утверждать, что в условиях воздействия на организм указанного компонента эпоксидных смол наблюдаются дезинтеграция герминативного эпителия семенников, умеренная вакуолизация клеток Лейдига и Сертоли, незначительное снижение индекса сперматогенеза, уменьшение секреции в предстательной железе и умеренное снижение высоты эпителия семенных пузырьков.

https://elibrary.ru/item.asp?id=30058305

48. 042889
Волошина И.С. ПОСЛЕДСТВИЯ ВЛИЯНИЯ ЭПИХЛОРГИДРИНА НА ВНУТРЕННИЕ ОРГАНЫ РЕПРОДУКТИВНОЙ СИСТЕМЫ КРЫС-САМЦОВ // Вятский медицинский вестник. 2018. № 1 (57). С. 16-22.

Целью данного исследования было изучение структуры внутренних органов репродуктивной системы самцов крыс после ингаляционного воздействия эпихлоргидрина на организм на микро- и ультрамикроскопическом уровнях. Экспериментальное исследование проводилось на 60 белых крысах-самцах, которые были введены в эксперимент в возрасте 12 недель с начальной массой 130-150 г. Крысы были разделены на контрольную и экспериментальную серии. Контрольная серия была представлена интактными крысами. Экспериментальная серия - I серия крыс, которые подвергались ингаляционному воздействию эпихлоргидрина в концентрации 10 мг/м3 в течение 60 дней, 5 дней в неделю, 5 часов в день. Окраска препаратов осуществлялась гематоксилином и эозином. Для электронно-микроскопического исследования использовали семенники и предстательную железу. Полутонкие срезы окрашивали 1% щелочным расствором толуидинового синего и исследовали с помощью светооптической системы «Olympus». Данные, полученные в ходе исследования, позволяют утверждать, что в условиях воздействия на организм указанного ксенобиотика стремительно развивается нарушение эндокринного статуса экспериментальных животных, которое проявляется в заметном торможении сперматогенеза на уровне образования сперматид...

https://elibrary.ru/item.asp?id=35080829

49. 025205
Григорьев Ю.Г., Чуешова Н.В., Верещако Г.Г СОСТОЯНИЕ РЕПРОДУКТИВНОЙ СИСТЕМЫ КРЫС-САМЦОВ В РЯДУ ПОКОЛЕНИЙ, ПОЛУЧЕННЫХ ОТ ОБЛУЧЕННЫХ РОДИТЕЛЕЙ И ПОДВЕРГНУТЫХ ЭЛЕКТРОМАГНИТНОМУ ВОЗДЕЙСТВИЮ ОТ МОБИЛЬНОГО ТЕЛЕФОНА // Медицинская радиология и радиационная безопасность. 2018. Т. 63. № 5. С. 33-40.

Цель: Изучить состояние репродуктивной системы крыс-самцов трех поколений (F1-F3), полученных от облученных родителей и подвергнутых ежедневной экспозиции от мобильного телефона (1745 МГц, 8 ч/сут) до достижения ими возраста 6 мес. Материал и методы: Белых крыс в возрасте 52-54 сут подвергали электромагнитной экспозиции от мобильного телефона (1745 МГц, 8 ч/сут, ППЭ 0,2-20 мкВт/см2, среднее значение 7,5±0,3 мкВт/см2) на протяжении 90 сут. Далее облученных самцов и самок спаривали в соотношении 1:2. Самок на протяжении всего периода беременности (20-21 сут) и полученное от них потомство (F1) продолжали облучать при вышеуказанном режиме до достижения возраста 6 мес. В возрасте 4 мес животные 1-го поколения (самцы и самки) спаривались для получения потомства 2-го поколения, а от них таким же образом получали потомство 3-го поколения. Состояние репродуктивной системы крыс-самцов трех поколений оценивали в возрасте 2, 4 и 6 мес..

https://elibrary.ru/item.asp?id=36357161

50. 041890
Демьяненко С.А., Марченко Н.В., Кириченко В.Н. ВЛИЯНИЕ КИШЕЧНОГО ЭНДОТОКСИНА НА ПОКАЗАТЕЛИ НЕСПЕЦИФИЧЕСКОГО ИММУНИТЕТА СЛИЗИСТОЙ ОБОЛОЧКИ РТА У КРЫС // Крымский терапевтический журнал. 2018. № 4. С. 34-37.

В статье приведены результаты анализа изменений биохимических показателей неспецифического иммунитета, происходящих в тканях слизистой оболочки полости рта у крыс. Эксперимент проведен на 90 крысах самках линии Вистар. Эндотоксинемию воспроизводили путем ежедневного внутримышечного введения 6,6 мкг/кг и 200 мкг/кг доз ЛПС из E. coli 0111:В4 в течение 14 дней. Животных выводили из опыта на 2, 4, 8 и 15-е сутки. Установлено, что достоверное увеличение цифровых значений степени дисбиоза в слизистой оболочке щеки и языка на 14 сутки эксперимента до 1,83 ± 0,19 ед (р<0,05) и до 9, 31± 0,96 ед (р<0,001), соответственно, является следствием достоверного снижения активности уреазы (р<0,05) и лизоцима (р<0,001), максимально выраженное при внутримышечном введении липополисахарида (ЛПС) в дозе 200 мкг/кг, что приводит к системной эндотоксинемии и поражению слизистой оболочки рта. Анализ цифровых значений степени дисбиоза слизистой оболочки рта указывает на снижение микробной обсемененности, причем, происходит это на фоне резкого снижения активности лизоцима. Наблюдаемые биохимические изменения в слизистой оболочке рта при внутримышечном введении ЛПС могут быть следствием вторичных реакций со стороны других органов, прежде всего, печени, ретикуло-эндотелиальная система которой чутко реагирует на присутствие в крови ЛП.С. Ключевые слова: воспалительные заболевания, дисбиоз, кишечный эндотоксин, системная эндотоксинемия, маркеры воспаления.

https://elibrary.ru/item.asp?id=36807152

51. PDF
Добрыня Ю.М., Тимченко Л.Д., Ржепаковский И.В., Бондарева Н.И., Писков С.И. ВЛИЯНИЕ БИОЛОГИЧЕСКИ АКТИВНОЙ СУБСТАНЦИИ ИЗ MEDUSOMYCES GISEVII (ЧАЙНЫЙ ГРИБ) НА ИММУНИТЕТ БЕЛЫХ КРЫС В УСЛОВИЯХ АН-ТИБИОТИКО-АССОЦИИРОВАННОГО ДИСБАКТЕРИОЗА // Ветеринарная патология. 2017. № 3 (61). С. 22-30.

Нормальная микрофлора желудочно-кишечного тракта выполняет огромный спектр функций. Одной из важнейших является ее участие в формировании, активизации и успешном функционировании иммунной системы. В результате воздействия ряда факторов естествен-ная микроэкология кишечника животного может нарушаться, что ведет к закономерному ос-лаблению функциональной активности нормофлоры, и, как следствие, к снижению резистент-ности организма. В связи с этим исследование было посвящено изучению параметров неспец-ифической резистентности (БАСК, КАСК, ЛАСК, ФИ, ФЧ, НСТ-тест спонтанный и индуциро-ванный) и иммунобиологической реактивности (уровень IgA, IgM, IgG, Т- и В-лимфоцитов) бе-лых крыс с экспериментально смоделированным антибиотико-ассоциированным дисбактерио-зом, а также под влиянием биологически активной субстанции из зооглеи природного симби-онта Medusomyces gisevii (чайный гриб), приготовленной согласно нашей технологии. Животным индуцировали дисбактериоз с помощью введения гентамицина сульфата перорально в течение 7-ми дней, после чего группа 2 получала дополнительно к основному корму субстанцию из зо-оглеи чайного гриба...

https://elibrary.ru/item.asp?id=32355682

52. PDF
Златник Е.Ю., Ситковская А.О., Шульгина О.Г., Бондаренко Е.С., Золотарева Е.И., Гречкин Ф.Н., Харагезов Д.А., Каймакчи Д.О. ВЛИЯНИЕ ВИРУСА БОЛЕЗНИ НЬЮКАСЛА НА ПОКАЗАТЕЛИ КЛЕТОЧНОГО ИММУНИТЕТА КРЫС-ОПУХОЛЕНОСИТЕЛЕЙ (ЭКСПЕРИМЕНТАЛЬНОЕ ИССЛЕДОВАНИЕ) // Современные проблемы науки и образования. 2018. № 4. С. 240.

Цель исследования - изучить морфо-патологические процессы, протекающие в органах иммунокомпетентной системы крыс при экспериментальном хламидиозе. Материалом для исследования служили патогенные микроорганизмы (хламидии). Опыты были проведены на крысах. Для заражения крыс использовали возбудитель Chl. Psittaci, штамм «Лори», выделенный в 1957 г. от попугая. Инфекционный материал животным вводился внутрибрюшинно в виде 10-процентной взвеси, очищенной дифференциальным центрифугированием овокультуры. Установлено, что в основе интранатального и постнатального патогенеза инфекции можно выделить несколько звеньев. Прохождение через родовые пути способствует попаданию возбудителя в организм новорождённого при прямом контакте с инфицированными эпителиальными клетками репродуктивных органов, далее происходит гематогенное распространение, включая иммунокомпетентные органы, которые утрачивают способность адекватно реагировать на инфекционное начало, затем дальнейшая фиксация в органах-мишенях с развитием той или иной клинико-морфологической формы заболевания.

https://elibrary.ru/item.asp?id=36345070

53. 041763
Корольков А.И., Калов А.Р., Атрощенко Е.В. НЕЙРОГУМОРАЛЬНАЯ РЕГУЛЯЦИЯ ПРОЦЕССОВ РЕМОДЕЛИРОВАНИЯ ЛЕВОГО ЖЕЛУДОЧКА ПРИ ПОСТИНФАРКТНОЙ АНЕВРИЗМЕ // Анналы хирургии. 2018. Т. 23. № 4. С. 205-210.

Одной из форм осложнения трансмурального инфаркта миокарда является развитие аневризмы левого желудочка. Процесс ремоделирования, заключающийся в прогрессирующей дилатации, деконфигурации левого желудочка, систолической и диастолической дисфункции, - это одна из основных причин развития хронической сердечной недостаточности. В представленном обзоре литературы рассмотрены патофизиологические основы, гуморальные системы регуляции постинфарктного ремоделирования левого желудочка и особенности вегетативной иннервации постинфарктного миокарда. Четкое понимание патогенеза патологического процесса в сердечной мышце вкаждом конкретном случае инфаркта миокарда позволяет выработать индивидуальный подход квыбору стратегии лечения пациента.

https://elibrary.ru/item.asp?id=36449390

54. 03652X
Кочетова О.В., Кумакшев А.С., Татарникова Н.А. ИММУНОМОРФОЛОГИЧЕСКАЯ ДИАГНОСТИКА ЭКСПЕРИМЕНТАЛЬНОГО ХЛАМИДИОЗА КРЫС В ОРГАНАХ ИММУНИТЕТА // Известия Оренбургского государственного аграрного университета. 2017. № 5 (67). С. 154-157.

Цель исследования - изучить морфо-патологические процессы, протекающие в органах иммунокомпетентной системы крыс при экспериментальном хламидиозе. Материалом для исследования служили патогенные микроорганизмы (хламидии). Опыты были проведены на крысах. Для заражения крыс использовали возбудитель Chl. Psittaci, штамм «Лори», выделенный в 1957 г. от попугая. Инфекционный материал животным вводился внутрибрюшинно в виде 10-процентной взвеси, очищенной дифференциальным центрифугированием овокультуры. Установлено, что в основе интранатального и постнатального патогенеза инфекции можно выделить несколько звеньев. Прохождение через родовые пути способствует попаданию возбудителя в организм новорождённого при прямом контакте с инфицированными эпителиальными клетками репродуктивных органов, далее происходит гематогенное распространение, включая иммунокомпетентные органы, которые утрачивают способность адекватно реагировать на инфекционное начало, затем дальнейшая фиксация в органах-мишенях с развитием той или иной клинико-морфологической формы заболевания.

https://elibrary.ru/item.asp?id=30547798

55. PDF
Марков И.И., Любаева Е.В. СПЛЕНЭКТОМИЯ - ВЛИЯЕТ ЛИ ОНА НА ИММУНИТЕТ И ПРОДОЛЖИТЕЛЬНОСТЬ ЖИЗНИ СТАРЫХ БЕЛЫХ КРЫС? // Морфологические ведомости. 2016. Т. 24. № 2. С. 36-46.

В результате возрастной инволюции селезёнка перестает выполнять функции периферического органа иммунной системы у людей пожилого и старческого возраста. Для клиники чрезвычайно важно выяснить к каким изменениям иммунитета и, естественно, продолжительности жизни может привести спленэктомия, выполненная у них по показаниям? Цель работы - провести сравнительную оценку морфологического статуса периферических органов иммунной системы и продолжительности жизни интактных и спленэктомированных старых белых крыс. Материал и методы исследования. На светооптическом и субмикроскопическом уровне изучена структура брыжеечных лимфатических узлов, большого сальника и печени у нелинейных спленэктомированных старых белых крыс (n=25). Контролем служили интактные старые белые крысы (n=7) одного возраста со спленэктомированными крысами. Результаты исследования свидетельствуют о выраженной иммунной стимуляции брыжеечных лимфатических узлов и большого сальника и увеличение продолжительности жизни спленэктомированных старых белых крыс на 4-6 месяцев по сравнению с интактными старыми белыми крысами.

https://elibrary.ru/item.asp?id=26284199

56. PDF
Николенко О.Ю. НАРУШЕНИЯ В КЛЕТОЧНОМ ИММУНИТЕТЕ И ОКСИДАНТНОАНТИОКСИДАНТНОЙ СИСТЕМЕ В МОДЕЛИ ПНЕВМОКОНИОЗА НА КРЫСАХ // Архив клинической и экспериментальной медицины. 2016. Т. 25. № 2. С. 121-126.

Для создания модели пневмокониоза на крысах им интратрахеально вводили суспензию угольно-породной пыли, после чего в корень хвоста вводили полный адъювант Фрейнда, а также азатиоприн и метилурацил. В эксперименте использованы две группы крыс-самцов линии «Вистар» с массой тела 200-250 г: 1 группа - здоровые животные (25 крыс), 2 группа - животные с моделированием пневмокониоза по полной схеме (25 крыс). Развитие аутоиммунных реакций и токсическое действие пыли были причиной значительных морфологических изменений структуры легких, характерных для пневмокониоза. Преимущества предложенного способа состояли в том, что заболевание развивается в наиболее короткий срок - 6 недель и требует меньших экономических затрат. При исследовании количества лейкоцитов у модельных животных оно было сниженным, наблюдался сдвиг лейкоцитарной формулы влево. Фагоцитарная активность нейтрофилов со стафилококком штамм 209 через 30 и 90 минут была сниженной. При исследовании оксидантной системы установлено достоверное повышение содержание диеновых конъюгатов и малонового диальдегида в сыворотке крови модельных животных...

https://elibrary.ru/item.asp?id=29799605

57. 039284
Узбякова Р.Р., Николаев А.А. ВЛИЯНИЕ СТРЕССОГЕННЫХ ФАКТОРОВ НА КОНФОРМАЦИОННЫЕ СВОЙСТВА БЕЛКОВ РЕПРОДУКТИВНОЙ СИСТЕМЫ САМЦОВ КРЫС // Международный журнал прикладных и фундаментальных исследований. 2016. № 12-6. С. 1013-1017.

Целью работы стало исследование эстеразной активности в репродуктивной системе самцов крыс, и снижение термолябмльности этих ферментов как показателя изменений их третичной структуры под влиянием токсических эффектов серводородсодержащего газа Астраханского газоконденсатного месторождения, низкоинтенсивного микроволнового излучения и пищевого и иммобилизационного стрессов. Экстракт ткани интактных крыс содержит очень высокий уровень эстеразной активности. По нашим данным в тесте расщепления альфа-нафтилацетата она составляет в среднем 1161,5±59,0 ЕД.и полностью инактивируется при 650С. Наибольшую термостабильность проявляет эстераза эпидидимисов и семенников крыс получавших облучение низкоинтенсивным микроволновым излучением, сохраняя 75% активности при 700С. Вероятно, в репродуктивной системе самцов крыс, получавших облучение низкоинтенсивным микроволновым излучением происходят конформационные сдвиги в молекулах ферментов, обеспечивающих эстеразную активность.

https://elibrary.ru/item.asp?id=27663490

58. 040578
Ярмолинская М.И., Тхазаплижева С.Ш., Молотков А.С., Флорова М.С., Денисова А.С., Траль Т.Г., Петросян М.А. ЭФФЕКТИВНОСТЬ МЕЛАТОНИНА В ЛЕЧЕНИИ ХИРУРГИЧЕСКИ ИНДУЦИРОВАННОГО ЭНДОМЕТРИОЗА У КРЫС // Проблемы репродукции. 2018. Т. 24. № 5. С. 33-40.

Цель исследования — оценить эффективность перорального приема мелатонина при лечении хирургически индуцированного эндометриоза у самок крыс линии Wistar. Материал и методы. В исследование включены 33 половозрелые самки крыс линии Wistar в возрасте от 10 до 12 нед. Всем экспериментальным животным выполнены 3 последовательные оперативные вмешательства. Этап 1-й — сформирована модель эндометриоза в процессе лапаротомии. Этап 2-й — через 2 нед от начала эксперимента проведена оценка образовавшихся очагов лапароскопическим доступом с последующей рандомизацией по группам. Основную группу составили 11 животных, которые получали мелатонин (препарат Мелаксен, «Unipharm Inc.», США) в течение 3 нед. В контрольную группу вошли 12 животных, не получавших лечение. В группу сравнения включены 10 животных, которые получали диеногест (препарат Визанна, «BAYER AG», Германия) в течение 3 нед. Этап 3-й — через 3 нед после начала лечения животных выводили из эксперимента и выполняли аутопсию, оценку, измерение и гистологическое исследование эндометриоидных очагов...

https://elibrary.ru/item.asp?id=36533466

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