[Kainate receptors in the hippocampus of rat strains with different levels of the nervous system excitability].

Glutamate receptors in the central nervous system play a significant role in the mechanisms of differential adaptation to the environmental conditions. However, structural and functional parameters of kainate receptors (KR) under normal conditions and during exposure to stress are not well characterized. Therefore, the aim of this research was to 1) study the distribution and the quantity of KR GluR 5/6/7 subunits; 2) examine their changes in the pyramidal cell layer of the hippocampus in rat strains with have genetically determined distinctions in the levels of nervous system excitability following the exposure to short-term emotional-painful stress; 3) estimate the sensitivity of hippocampal pyramidal neurons to the action of KR agonist -kainic acid. It was demonstrated that GluR 5/6/7 KR are localized mainly in the region of hippocampal CA2 area; in the animals with low excitability their quantity was greater than in those with high excitability. Short-term emotional-painful stress resulted in the increase of KR in hippocampal CA2 area only in highly excitable rats. Selective sensitivity of pyramidal neurons in different hippocampal fields to the action of kainic acid was demonstrated and it was found to depend on animal strain characteristics of of the nervous system excitability.

[Systemic control of the molecular, cell, and epigenetic mechanisms of long-lasting consequences of stress].

Based on M.E. Lobashev's views of the systemic control of genetic and cytogeneitc processes and a substantial effect of excitability on plastic changes in the central nervous system (CNS), the effect of prolonged emotional and pain stress (PEPS) on the molecular, cell, and epigenetic mechanisms of injury memory was studied in rat strains bred for a certain excitability of the nervous system. PEPS was for the first time found to cause long-lasting (2 months) morphological alterations of the CA3 region of the hippocampus and to modify the genome activity of its pyramidal neurons. The two phenomena were potentiated by a genetically determined low functional state of the CNS. The post-stress regulation of the genome function in hippocampal neurons was mediated by changes in heterochromatin conformation, activation of methyl-CpG-binding protein (MeCP2) synthesis, and subsequent changes in acetylation of histone H4. Genetically determined high excitability of the nervous system proved to be a risk factor that affects the specifics and time course of the observed molecular, cell, and genetic transformations of neurons. The results provide for a better understanding of the epigenetic mechanisms of injury memory, which forms a pathogenetic basis for posttraumatic stress disorder and other human psychogenic conditions characterized by a prolonged duration.

[Heterochromatin characteristics in hippocampal neurons of rats with different excitability of the nervous system under conditions of posttraumatic stress disorder modeling].

Two lines of rats, selected according to the excitability of nervous system to the action of an electric current, served as the model objects to study the changes of heterochromatin characteristics in neurons of hippocampus (area CA3) 24 hours, 2 weeks, 2 and 6 months after exposure to prolonged emotional painful stress. It was shown that exposure to stress caused changes in the area, occupied by heterochromatin, only in rats with low-excitability: it was decreased 24 hours, 2 weeks and 2 months following the stress, while it was increased after 6 months as compared to control values. Thus, it was demonstrated for the first time that long-term modifications of heterochromatin structural characteristics of neurons in hippocampus (area CA3) could depend on genetically determined functional state of the nervous system.

[Architecture of the X chromosome, expression of LIM kinase 1, and recombination in the agnostic mutants of Drosophila: a model of human Williams syndrome]. / Osobennosti arkhitektury X-khromosomy, ékspressii LIM kinazy 1 i rekombinatsii u mutantov drozofily lokusa agnostic: model' sindroma uil'iamsa cheloveka.

As the Human Genome and Drosophila Genome Projects were completed, it became clear that functions of human disease-associated genes may be elucidated by studying the phenotypic expression of mutations affecting their structural or functional homologs in Drosophila. Genomic diseases were identified as a new class of human disorders. Their cause is recombination, which takes place at gene-flanking duplicons to generate chromosome aberrations such as deletions, duplications, inversions, and translocations. The resulting imbalance of the dosage of developmentally important genes arises at a frequency of 10(-3) (higher than the mutation rate of individual genes) and leads to syndromes with multiple manifestations, including cognitive defects. Genomic DNA fragments were cloned from the Drosophila melanogaster agnostic locus, whose mutations impair learning ability and memory. As a result, the locus was exactly localized in X-chromosome region 11A containing the LIM kinase 1 (LIMK1) gene (CG1848), which is conserved among many species. Hemizygosity for the LIMK1 gene, which is caused by recombination at neighboring extended repeats, underlies cognitive disorders in human Williams syndrome. LIMK1 is a component of the integrin signaling cascade, which regulates the functions of the actin cytoskeleton, synaptogenesis, and morphogenesis in the developing brain. Immunofluorescence analysis revealed LIMK1 in all subdomains of the central complex and the visual system of Drosophila melanogaster. Like in the human genome, the D. melanogaster region is flanked by numerous repeats, which were detected by molecular genetic methods and analysis of ectopic chromosome pairing. The repeats determined a higher rate of spontaneous and induced recombination. including unequal crossing over, in the agnostic gene region. Hence, the agnostic locus was considered as the first D. melanogaster model suitable for studying the genetic defect associated with Williams syndrome in human.

[Characteristics of heterochromatin of heterophase nuclei from interphase neurons of various brain structures selected for the nervous system excitability]. / Kharakteristika geterokhromatina interfaznykh iader neironov razlichnykh struktur golovnogo mozga krys, selektirovannykh po vozbudimosti nervnoi sistemy.

Quantitative characteristics (the area and number of chromocenters) of the interphase C-heterochromatin in the nuclei of pyramidal neurons of the midbrain reticular formation, sensorimotor cortex, and hippocampus (CA3) of rat strains with different genetically determined excitability were studied in the normal state of the animals and after exposure to a short-term emotional pain stress. The results indicate a relationship between the excitability of the nervous system and structural-functional state of the neuronal interphase heterochromatin. The role of cytogenetic features of different brain structures in the CNS functioning and behavior and their relation with genetically determined excitability of the nervous system are discussed.

[Effect of prenatal emotional-pain stress on the status of interphase chromatin in neurons of the rat developing brain with various excitation of the nervous system]. / Vliianie prenatal'nogo émotsional'no-bolevogo stressa na sostoianie interfaznogo khromatina v neironakh razvivaiushchegosia mozga krys s razlichnoi vozbudimost'iu nervnoi sistemy.

A short-term emotional-painful stress, experienced by pregnant rat females differing in threshold of excitability of their nervous system, was used to assess the state of interphase condensed chromatin and C-heterochromatin of neuron nuclei in developing brains of 16-17 day old embryos. To reveal relationships between the genetically determined excitability of rats and the state of interphase chromatin in their neuron nuclei a computer information system has been used that enabled us to classify the neuronal nuclei according to their specific DNA image cytometry features. The results indicate an obvious relationship between excitability of the nervous system and structural-functional state of the neuronal interphase chromatin.

[Proliferative activity and structure-functional organization of chromosomes in cells from the developing brain in respect to genetically determined excitability of the rat nervous system]. / Proliferativnaia aktivnost' i osobennosti strukturno-funktsional'noi organizatsii khromosom v kletkakh razvivaiushchegosia mozga v sviazi s geneticheski determinirovannoi vozbudimost'iu nervnoi sistemy u krys.

Neuroblasts of developing hippocampus of 16-17-day old rat embryo of the line with high threshold excitability are characterised by a high level of proliferative activity and chromosome aberration, as well as high degree of brain chromatin concentration as compared with embryos of a line with low threshold excitability.

[An information system for automated cytogenetic image processing: analysis of interphase chromatin of nerve cells of embryonic brain of rats with varying nervous system excitability]. / Informatsionnaia sistema dlia avtomaticheskoi obrabotki tsitogeneticheskikh dannykh: analiz interfaznogo khromatina nervnykh kletok mozga émbrionov krys s razlichnoi vozbudimost'iu nervnoi sistemy.

To reveal a relationship between the genetically determined excitability of rats and the structural-functional chromosome organization in their neurone nuclei a computer information system has been developed to classify the neurone nuclei according to their specific DNA image cytometry features. The nuclear features, such as size, shape, and DNA content, are calculated, along with features describing characteristics of chromatin with the nucleus. The neural and glial cells are separated according to the rule based expert system approach with the use of a nuclear feature vector. The DNA image processing is performed and a feature vector consisting of normalized measures of the neurone nucleus chromatin region descriptors is extracted. The results indicate a relationship between the peculiarities of the nervous system and the structural-functional state of the chromosomal apparatus.

[Structural-functional chromosome organization in response to stress]. / Issledovanie strukturno-funktsional'noi organizatsii khromosom pri reaktsii na stress.

Published data and the results of experiments conducted at the Laboratory of Genetics of Higher Nervous Activity, Pavlov Institute of Physiology, on the effect of stress on chromosome structure and function are reviewed briefly. Experiments were performed on inbred rats selected for excitation threshold and mutant Drosophila with altered metabolism of secondary mediators.

[Frequency of chromosome aberrations induced by stress and cyclophosphane in bone marrow cells of rats selected for the threshold of nervous system excitability]. / Chastota khromosomnykh aberratsii, indutsirovannykh stressornym vozdeistviem i tsiklofosfanom v kletkakh kostnogo mozga krys, selektirovannykh po porogu vozbudimosti nervnoi sistemy.

The frequency of chromosomal aberrations in bone marrow cells under the effect of long-term stress and cyclophosphamide was studied in rat lines selected for different levels of nervous system excitability. After both kinds of treatment, differences between lines in frequencies of chromosomal aberrations were observed. Stress had a weak mutagenic effect on rats with a low level of excitability, but no such effect on highly excitable rats. Correlations between cytogenetic parameters of chromosomal aberrations induced by cyclophosphamide and the functional state of the nervous system were ambiguous. Thus, the frequency of single and paired chromosome fragments did not show any apparent correlation with the excitability of animals. The frequency of translocation-like chromosomal interchanges in highly excitable rats was higher than in weakly excitable rats. In terms of the number of cells with aberrations, a dependence of the type of interlinear differences on the selection program was observed. Possible mechanisms responsible for differences in susceptibility of animals to the action of mutagenic factors are discussed in relation to peculiarities of the functional state of the nervous system in the studied lines.

[The role of testosterone in regulating the aggressive behavior of male laboratory mice of different strains]. / Rol' testosterona v reguliatsii agressivnogo povedeniia samtsov laboratornykh myshei razlichnykh linii.

The influence of testosterone on aggressive behaviour, on urinal pheromonal activity, on weight of the preputial gland, seminal vesicles and coagulating glands of male mouse CBA, C57BL/6 and hybrids CBAB6F1 was studied. The interstrain differences in reactivity to testosterone in aggressive behaviour tests and in seminal vesicles and coagulating gland weight were found. The urinal pheromonal characteristics were not changed by testosterone influence. No significant correlations between the aggressive behaviour parameters, urinal pheromonal activity, testosterone plasma levels and reactivity to its action were discovered.

[Corticosteroid response and indolamine content of the mouse brain under the action of a pheromone, disrupting spermatogenesis]. / Kortikosteroidnyi otvet i soderzhanie indolaminov v mozge myshei pri deìstvii feromona, narushaiushchego spermatogenez.

The volatile components of adult male urine from laboratory mice of CBA/LacSto strain inhibited spermatogenesis in CBAB6F1 30-day old mice. There were no significant responses in hypothalamic and olfactory bulb indolamine systems, neither in the blood corticosterone level of the mice during experimental treatment. A prolactin mechanism of the pheromone inhibition of testicular function is suggested.