Search

Chronic stress is a risk factor for major depression. Social defeat stress is a well-validated murine model of depression. However, little is known about the gene activity dynamics during the development of a depression-like state. We analyzed the effects of social defeat stress of varying duration (10 and 30 days) on the behavioral patterns and prefrontal-cortex transcriptome of C57BL/6 mice. The 10-day exposure to social defeat stress resulted in a high level of social avoidance with no signs of depression-associated behavior. Most animals exposed to 30 days of social defeat stress demonstrated clear hallmarks of depression, including a higher level of social avoidance, increased immobility in the forced swimming test, and anhedonic behavior. The monitoring of transcriptome changes revealed widespread alterations in gene expression on the 10th day. Surprisingly, the expression of only a few genes were affected by the 30th day of stress, apparently due to a reversal of the majority of the early stress-induced changes to the original basal state. Moreover, we have found that glucocorticoid-sensitive genes are clearly stimulated targets on the 10th day of stress, but these genes stop responding to the elevated corticosterone level by the 30th day of stress. The majority of genes altered by the 30-day stress were downregulated, with the most relevant ones participating in chromatin modifications and neuroplasticity (e.g., guanine nucleotide exchange factors of the Rho-family of GTPases). Very different molecular responses occur during short-term and long-term social stress in mice. The early-stress response is associated with social avoidance and with upregulation and downregulation of many genes, including those related to signal transduction and cell adhesion pathways. Downregulation of a few genes, in particular, genes for histone-modifying methyltransferases, is a signature response to prolonged stress that induces symptoms of depression. Altogether, our data show that the development of depression under social stress conditions is correlated with suppression of the overactive molecular response to induced stress, involving gene regulatory resistance to glucocorticoid molecules, potentially via a chromatin remodeling mechanism.

Unlabelled: Chronic social defeat stress leads to the development of mixed anxiety-depression state, which accompanied by immune deficiency in male mice. Paper aimed to study effects of ronkoleukin on the parameters of cellular immunity in the thymus and spleen and psychoemotional state in these animals., Methods: Mixed anxiety/depression state was produced by chronic social defeat stress during 20 days in male mice. Roncoleukin (5000 ME/kg, i/p) and saline were chronically injected to depressive mice during 2 weeks without agonistic interactions. After this period subpopulations of lymphocytes in the thymus and spleen were studied in male mice. The animals were also studied in behavioral tests estimating the levels of communicativeness, anxiety and depressiveness., Results: Roncoleukin decreases the number of lymphocytes in the thymus and spleen, and increased the number of lymphocytes in blood and thymus index. Medication increased per cent of CD4+8+ lymphocytes in the thymus and per cent of CD8+ and CD3+25- lymphocytes in the spleen. Roncoleukin induced anxiogenic, stimulative and antidepressive effects., Conclusion: Roncoleukin has small efficacy for treatment of immune suppression induced by chronic social defeat stress and has anxiogenic, stimulating and weak antidepressive effects.

Chronic psychoemotional stress of social defeats produces development of experimental anxious depression in male mice similar to this disorder in humans. 5-HT and 5-HIAA levels, TPH and MAO A activities, 5-HT1A-receptors in different brain areas were investigated at different stages of development of experimental disorder. It has been shown that initial stage (3 days of social stress) is accompanied by increase of 5-HT level in some brain areas. Decreased 5-HIAA levels in the hippocampus, amygdala and nucleus accumbens were discovered at the stage of forming depression (10 days of social stress). Pharmacological desensitisation and decreased number of 5-HT1A-receptors were shown in frontal cortex and amygdala. At the stage of pronounced depression (20 days of stress), there were no differences in 5-HT and 5-HIAA levels in all brain areas (excluding hypothalamus) of depressive animals. However increased number of 5-HT1A-receptors and decreased affinity in amygdala and decreased TPH and MAOA activities in hippocampus were found in depressive mice. Hypofunction of serotonergic system is suggested at the stage of pronounced depression state in animals. Similar processes had place in brain dopaminergic systems. It is concluded that dynamic changes of brain monoaminergic activities accompany the development of anxious depression in animals. Various parameters of monoaminergic systems are differently changed depending on brain area, mediator system and stage of disorder.

The aim of this work was to examine the behavioral effects of a novel lithium-based enterosorbent, Noolit (665 mg/kg), on male mice with mixed depression/anxiety-like state evoked by exposure to repeated social defeats in daily agonistic confrontations. The lithium component allows Noolit to be used as a psychotropic drug. Two experiments are described, in which the therapeutic and preventative effects of chronic Noolit treatment were examined. Response to Noolit was assessed in the plus maze, open field, partition test, and Porsolt's test. In both experiments, Noolit produced obvious anxiolytic and antidepressant effects. Treatment with Noolit fully restored some behavioral parameters in the plus maze and open field in depressed mice and prevented depression that would otherwise have developed. It has been suggested that enterosorbent Noolit can be a potent drug for the treatment of mixed anxiety/depression pathologies and for prevention of mood disorders.

Protective properties of a new enterosorbent noolith (lithium ions immobilized on mineral matrix) were studied in C57Bl/6J mice predisposed to depression caused by intermale confrontations. The drug was administered daily for 15 days after the 5th confrontation and then the animals were tested in the forced swimming test. The number of specific(3)H-8-OH-DPAT binding sites in 3 brain regions was determined. It is shown that noolith produced an antidepressive effect manifested in decreased immobility time in the Porsolt test. Moreover, noolith reduced the number of 1A-serotonin receptors in the frontal cortex and hypothalamus. It is concluded that noolith possesses protective properties.

The enterosorbent noolit (representing a mineral matrix base with immobilized lithium and silicon compounds) significantly affects the psychoemotional state of mice with depression model induced by prolonged social emotional stress. Noolit administration produces a pronounced anxiolytic and antidepressant effect and reduced the level of behavioral deficiency in the test animals.