Publications by authors named "Khotskin N"

Parkinson's disease (PD) is an age-related neurodegenerative pathology of the central nervous system. The well-known abnormalities characteristic of PD are dysfunctions in the nigrostriatal system including the substantia nigra of the midbrain and the striatum. Moreover, in PD persons, alpha-synucleinopathy is associated with abnormalities in the dopaminergic brain system.

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Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor because it does not bind to a known specific receptor on the plasma membrane and functions primarily as an unfolded protein response (UPR) regulator in the endoplasmic reticulum. Data on the effects of CDNF on nonmotor behavior and monoamine metabolism are limited. Here, we performed the intracerebroventricular injection of a recombinant CDNF protein at doses of 3, 10, and 30 μg in C57BL/6 mice.

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Topologically associated domains (TADs) restrict promoter-enhancer interactions, thereby maintaining the spatiotemporal pattern of gene activity. However, rearrangements of the TADs boundaries do not always lead to significant changes in the activity pattern. Here, we investigated the consequences of the TAD boundaries deletion on the expression of developmentally important genes encoding tyrosine kinase receptors: Kit, Kdr, Pdgfra.

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Tryptophan hydroxylase 2 (TPH2) is the key and rate-limiting enzyme of serotonin (5-HT) synthesis in the mammalian brain. The 1473G mutation in the Tph2 gene decreases TPH2 activity in the mouse brain by twofold. (R)-2-amino-6-(1R, 2S)-1,2-dihydroxypropyl)-5,6,7,8-tetrahydropterin-4(3H)-one (BH) is a pharmacological chaperone for aromatic amino acid hydroxylases.

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Cerebral dopamine neurotrophic factor (CDNF) is a promising agent for Parkinson's disease treatment. However, its role in regulation of non-motor behavior including various psychopathologies remains unclear. In this regard, the aim of the present work was to study effect of CDNF overexpression in hippocampus on behavior of the ASC mice (Antidepressant Sensitive Cataleptics) with genetic predisposition to depressive-like behavior.

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Aim: The peripheral tumor growth is accompanied by the accumulation of inflammatory mediators in the blood that can negatively influence blood-brain barrier function and neuronal structure and develop the cancer-associated depression. The aim of the study was to evaluate the neurobiological effects of lithium on hepatocellular carcinoma mice model.

Methods: In this study we analyzed the locomotor activity of lithium-treated tumor-bearing mice using the Phenomaster instrument.

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To identify body systems subject to epigenetic transformation during in vitro fertilization (IVF), comparative morphological and functional studies were performed on sexually mature offspring of outbred CD1 mice, specific-pathogen-free (SPF), obtained by IVF (experiment) and natural conception (control). The studies included assessment of age-related changes in body weight and composition, energy intake and expenditure, and glucose homeostasis. To level the effects caused by the different number of newborns in the control and in the experiment, the size of the fed litters was halved in the control females.

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Tryptophan hydroxylase 2 (TPH2) is the key and rate-limited enzyme of serotonin (5-HT) synthesis in the brain. The mutation in the gene results in a two-fold decrease in enzyme activity in the mouse brain. The () mutation in the locus results in the overexpression of the gene in the brain and causes obesity and depressive-like behavior in mice.

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Tryptophan hydroxylases 1 and 2 (TPH1 and TPH2) play a key role in the synthesis of serotonin (5-HT), a hormone and neurotransmitter, in the peripheral organs and brain, respectively. The main aim of this study was to clarify the distribution of mRNA of the Tph1 and Tph2 genes in brain structures under normal conditions and after inflammation. The experiments were carried out on young (4 weeks old) male C57BL/6 mice.

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Background: The brain melanocortin system regulates numerous physiological functions and kinds of behavior. The agouti protein inhibits melanocortin receptors in melanocytes. The (A) mutation puts the gene under the control of the gene promotor and causes the agouti protein expression in the brain.

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Here, we present the first evidence for brain adaptation in pigs tolerant to the human presence, as a behavioral trait favoring domestication. The study was carried out on minipiglets from population bred at the Institute of Cytology and Genetics (Novosibirsk, Russia). We compared the behavior, metabolism of monoaminergic neurotransmitter systems, and functional activity of the hypothalamic-pituitary-adrenal system, as well as neurotrophic markers in the brain of minipigs differing by tolerance to human presence (HT and LT - high and low tolerance).

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We studied the effect of the C1473G polymorphism in the Tph2 gene that reduces the activity of the tryptophan hydroxylase 2 in the brain on the severity of changes in motor activity (23 h after intraperitoneal administration of 0.8 mg/kg LPS or saline) and on the level of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the endings of 5-HT neurons in the cortex, hippocampus, and striatum (24 h after administration) of mature male mice of congenic lines B6-1473CC (high activity) and B6-1473GG (low activity). The state of the immune system in these structures was assessed by the expression of genes for proinflammatory cytokines IL-1β and TNF.

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Autism spectrum disorders (ASDs) are some of the most common neurodevelopmental disorders; however, the mechanisms underlying ASDs are still poorly understood. Serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) are known as key players in brain and behavioral plasticity and interact with each other. 5-HT receptor is a principal regulator of the brain 5-HT system, which modulates normal and pathological behavior.

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Vavilovskii Zhurnal Genetiki i Selektsii = Vavilov Journal of Genetics and Breeding. 2019;23(5):582-587 (in Russian) Page 587, in Acknowledgements instead of The animals and behavioral testing are supported by the budget project (No. 0324-2019-0041).

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This study aimed to assess the sex differences in the feeding behaviour of non-obese diabetic severe combined immunodeficient (NOD SCID) mice in a pharmacological model of type 1 diabetes mellitus (T1Dm). In our study, we chose NOD SCID mice of both sexes and assessed their feeding behaviour, body weight, body fat and water content under identical experimental conditions and diets. After 1 month of diabetes mellitus in mice in the experimental group, males and females did not show any increase in body weight, and they weighed significantly less than the control group.

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Variations in anxiety-related behavior are associated with individual allostatic set-points in chronically stressed rats. Actively offensive rats with the externalizing indicators of sniffling and climbing the stimulus and material tearing during 10 days of predator scent stress had reduced plasma corticosterone, increased striatal glutamate metabolites, and increased adrenal 11-dehydrocorticosterone content compared to passively defensive rats with the internalizing indicators of freezing and grooming, as well as to controls without any behavioral changes. These findings suggest that rats that display active offensive activity in response to stress develop anxiety associated with decreased allostatic set-points and increased resistance to stress.

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Male C57Bl/6J mice were exposed to daily 24-h illumination over 14 days and daily intragastrically received melatonin (1 mg/kg) or water (placebo). Controls were kept under standard day/night (14/10 h) conditions. Melatonin prevented the development of anemia in mice exposed to continuous illumination, which was proven by higher blood hemoglobin levels by the end of the experiment in melatonin-treated animals in comparison with the placebo group.

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We studied the influence of obesity caused by lethal yellow (A) mutation in the agouti gene, short photoperiod (4/20 h light/darkness), and combination of these factors on depressive-like behavior in the forced swimming test and expression of genes encoding proinflammatory cytokines in the hypothalamus of heterozygous male C57Bl/6-A/a mice and their wild-type littermate controls (C57Bl/6-a/a). It was shown that A mutation as well as short photoperiod increased depressive-like behavior in mice. No effect of the interaction of A mutation and photoperiod on immobility in the forced swimming test was revealed.

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The concepts of allostatic load and overload, i. e., a dramatic increase in the allostatic load that predisposes to disease, have been extensively described in the literature.

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Reduction of natural illumination in fall/winter months causes seasonal affective disorders (SAD) in vulnerable individuals. Neurotransmitter serotonin (5-HT) is involved in the mechanism of SAD. Tryptophan hydroxylase-2 (TPH2) is the key enzyme of 5-HT synthesis in the brain.

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Lethal yellow (A) mutation causes obesity and type-2 diabetes in mice. Here we studied the effect of the A mutation on the brain and behavior. The experiments were carried out on adult (11-12 weeks old) males of A/a mice and their wild-type littermates (a/a).

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The serotoninergic 5-HT receptor is involved in the mechanism of depression and antidepressant drugs action. Earlier we showed that striatal-enriched protein tyrosine phosphatase (STEP) inhibitor - 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (TC-2153) affects both the brain serotoninergic system and the brain-derived neurotropic factor that are known to be involved in the psychopathology of depression. In the present study we investigated the effects of chronic TC-2153 administration on behavior in the standard battery of tests as well as the effects of acute and chronic TC-2153 treatment on the brain 5-HT receptors in mice.

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Neurotransmitter serotonin (5-HT) is involved in the regulation of stress response. Tryptophan hydroxylase-2 (TPH2) is the key enzyme of serotonin (5-HT) synthesis in the brain. C1473G polymorphism in Tph2 gene is the main factor defining the enzyme activity in the brain of laboratory mice.

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The description of the installation with inverted light is given as well as its software EthoStudio, which allows tracking the movements of any color animal in the water Morris maze (WMM) in high definition. The installation is based on the transmitted light technology (inverted light). The software gives possibility to estimate a wide range of learning indices.

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The effect of glial cell line-derived neurotrophic factor (GDNF) on behavior and brain dopamine system in predisposed to depressive-like behavior ASC (Antidepressant Sensitive Cataleptics) mice in comparison with the parental "nondepressive" CBA mice was studied. In 7days after administration (800ng, i.c.

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