The Effect of Long-Term Emotional and Painful Stress on the Expression of Proinflammatory Cytokine Genes in Rats with High and Low Excitability of the Nervous System.

Stress plays an important role in the pathogenesis of anxiety and depressive disorders. Neuroinflammation is considered as one of the mechanisms by which stress alters the molecular and cellular plasticity in the nervous tissue and thus entails CNS dysfunction. The contribution of genetically determined features of the nervous system to the development of post-stress neuroinflammation has not been sufficiently studied. In this study, the dynamics of post-stress changes in mRNA levels of the il-1ß and tnf genes encoding proinflammatory cytokines interleukin-1 beta (IL-1ß) and tumor necrosis factor (TNF) were evaluated in the blood and brain of two rat strains with high and low excitability thresholds of the nervous system (HT and LT, respectively). Changes in IL-1ß and TNF mRNA levels were assessed by real-time PCR 24 h, 7, 24 and 60 days after long-term long-term emotional and painful stress in the blood and three brain structures involved in the development of post-stress pathology (prefrontal cortex, hippocampus, amygdala). In highly excitable LT rats, IL-1ß mRNA level in the hippocampus and amygdala increased compared to the control 24 days after stress termination, while in low-excitable HT animals, an increase in the level of IL-1ß mRNA was only detected in the hippocampus at the same time point. TNF mRNA level did not change in any of the rat strains at any of the post-stress time points. Genetically determined excitability of the nervous system is a promising marker of individual stress vulnerability, as manifested in post-stress disorders associated with developmental and time-course features of neuroinflammation.

[Changes in Expression of Genes Associated with Calcium Processes in the Hippocampus in Mice Exposed to Chronic Social Stress].

Whole-transcriptome data were used to study the changes in expression of genes coding proteins involved in the calcium regulation processes in the hippocampus of male mice with symptoms of depression caused by chronic social defeat stress. Cacna1g, Cacnb3, Camk1g, Camk2d, Camk2n2, Caly, Caln1, S100a16, and Slc24a4 genes were upregulated in the hippocampus of depressed mice compared to a control, while Cacna2d1, Cacng5, Grin2a, and Calm2 were downregulated. The greatest number of significant correlations was observed between the expression level of Calm2, which showed the highest transcriptional activity, and other differentially expressed genes. Calcium signaling in the hippocampus was assumed to be disrupted in mice exposed to chronic social defeat stress. The involvement of Calm2, Camk1g, Camk2d, and Camk2n2 genes in the process is discussed.

Effect of long-term stress on H3Ser10 histone phosphorylation in neuronal nuclei of the sensorimotor cortex and midbrain reticular formation in rats with different nervous system excitability.

The effects of long-term mental and pain stress on H3Ser10 histone phosphorylation in neurons of the the sensorimotor corex and midbrain reticular formation were studied 24 h, 2 weeks, and 2 months after exposure of rats differing by the nervous system excitability. Rats with high excitability threshold exhibited higher basal level of H3Ser10 histone phosphorylation in the midbrain reticular formation neurons than rats with low excitability threshold. The sensorimotor cortical neurons of the two strains did not differ by this parameter. Stress led to a significant increase in the counts of immunopositive neuronal nuclei in rats with low excitability threshold: the parameter increased significantly in the sensorimotor cortex 24 h after exposure and normalized in 2 weeks after neurotization. In the midbrain reticular formation of this rat strain stress stimulated H3Ser10 histone phosphorylation after 24 h and after 2 weeks; the parameter normalized after neurotization in 2 months. Hence, genetically determined level of the nervous system excitability was essential for the basal level of neuron phosphorylation and for the time course of this process after long-term exposure to mental and pain stress, depending on the brain structure. A probable relationship between H3Ser10 histone phosphorylation process and liability to obsessive compulsive mental disorders in humans was discussed.

Effect of chronic emotional and pain stress on histone H3 phosphorylation in the hippocampus of rat strains with different excitability of the nervous system.

Long-term effects of chronic emotional and pain stress on histone H3 phosphorylation by serine 10 in hippocampal CA3 neurons were examined 24 h, 2 weeks, and 2 months after termination of the stress procedure in 2 rat strains differing by excitability of the nervous system. The low excitable rats with high threshold (HT) of excitability were characterized by a high baseline level of histone H3 phosphorylation in comparison with the high excitable rats with low threshold (LT) of excitability. The long-term emotional and pain stress significantly changed the number of positive immune cells in highly excitable rats: this parameter increased in 24 h and 2 weeks after the stress, but returned to the control level in 2 months. In contrast, stress did not affect histone H3 phosphorylation in low excitable rats. Thus, long-term (up to 2 weeks) changes in histone H3 phosphorylation were reveled in rat hippocampal CA3 neurons, which depended on genetically determined functional status of the nervous system.

Long-term effects of prenatal stress on the characteristics of hippocampal neurons in rats with different excitability of the nervous systems.

We studied the effects of prenatal emotional painful stress on numerical density of neurons and characteristics of heterochromatin in developing and mature hippocampus of rats with different excitability of the nervous systems. It was shown that prenatal stress reduces the numerical density of neurons in hippocampal CA3 field in 24-day-old and adult (3 months) low excitable animals and chromocenter area in cells of developing hippocampus in embryos of both strains. The difference in chromocenter areas in offspring of stressed females was retained on postnatal day 24.

[A comparative study of the taste sensitivity to phenylthiocarbamide in rats differing by the threshold of nervous system excitability]. / Sravnitel'noe izuchenie vkusovoi chuvstvitel'nosti k feniltiokarbamidu u krys, razlichaiushchikhsia po progu vozbudimosti nervnoi sistemy.

Taste sensitivity to a bitter substance, phenylthiocarbamide (PTC) was studied in rat strains selected for the threshold of excitability of the nervous system. In the period of 17 days the drinking behaviour of the rats was estimated after giving them a series of PTC solutions with increasing concentrations and water as a control. The interstrain differences were found in the mean level of this index and its dynamics during the experimental period. Rats of the strain with high excitability showed the rhythmical changes of taste sensitivity to PTC related to the phases of moon rhythm. The obtained evidence points to relation between the sign under study and individual characteristics of the nervous system, namely, its excitability, and suggests the differences in activity of the second messenger system (Ca++, c-AMP and others) in the studied rat strains.

[Effect of genetic background on mutation frequency of insertional alleles of the lozenge in Drosophila melanogaster]. / Vliianie geneticheskogo fona na chastotu mutirovaniia insertsionnykh alleli gena lozenge u Drosophila melanogaster.

We studied the effect of genetic background on mutation frequency of an unstable lz75V allele of the lozenge gene (lz; 1-27.7) isolated from natural populations of Drosophila melanogaster and its mutant derivatives lzB abd lzsl. Genetic composition of the X chromosome containing unstable alleles (X75V chromosome) was shown to affect their mutability. The region of the chromosome proximal to lozenge contains factors required for high mutability of lz75V and lzB. Substitution of a distal part of the X chromosome from a laboratory strain for a homologous part of the X75V chromosome also resulted in stabilizing lz75V, but caused an increase in mutation frequency of lzB. Association between instability of lz75V and the presence of P element with the locus was revealed by in situ hybridization. Studying effects of regulatory elements from a pi 2 P strain showed that the P cytotype is associated with a twofold to threefold decrease in mutation frequency of lzB and lzsl, but P-M hybrid dysgenesis is associated with its slight increase. Regulation of instability of the lozenge gene within the X75V chromosome was assumed to involve three levels: (1) character and topography of a mobile element inserted into the locus, (2) regulatory factors of other X-chromosomal regions, and (3) cytoplasmic factors. The results obtained are discussed in terms of regulation of transposition of mobile genetic elements.

[The ontogenetic characteristics of the motor exploratory reaction of female laboratory mice during exposure to the urinary pheromones of sexually mature males]. / Ontogeneticheskie osobennosti dvigatel'noi issledovatel'skoi reaktsii samok laboratornykh myshei pri vozdeistvii feromonov mochi polovozrelykh samtsov.

Motor exploratory activity of 36 and 41 days old female laboratory mice CBA and C57BL/6 and their hybrids CBAB6F1 was studied after the action of urine of male mice CBA and C57BL/6. Five parameters were recorded. It was shown that formation of behavioural response to the socially important stimulus of pheromonal nature occurred during puberty process depending on the donor and recipient genotypes and on the previous experience of interaction with the stimulus. The critical period of formation of this reaction was revealed in the ontogeny of females.

[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.