Molecular implications of prolonged aggression experience: Th, Dat1, Snca and Bdnf gene expression in the ventral tegmental area of the victorious male mice

Th, Dat1, Snca and Bdnf were the genes whose mRNA levels in the ventral tegmental area of the midbrain were measured in male mice that were victorious in 20 daily agonistic interactions and in a group of such victorious mice that had later not been allowed to fight for 14 days. This experiment demonstrated increased Th, Dat1 and Snca but not Bdnf mRNA levels in the former group as compared to the controls. In the latter group, the expression of the Th and Dat1 genes was still enhanced, while the level of Snca mRNA did not differ from that in the controls. These findings suggest that positive fighting experience enhances the expression of the genes concerned with dopaminergic systems and this enhanced expression is preserved for a long time afterwards. Significant positive correlations were found between the level of aggression and Th and Snca mRNA levels in the winners

Snca and Bdnf gene expression in the VTA and raphe nuclei of midbrain in chronically victorious and defeated male mice

The study aimed to analyze the mRNA levels of Snca and Bdnf genes in the ventral tegmental area (VTA) and raphe nuclei of the midbrain in male mice that had each won or defeated 20 encounters in daily agonistic interactions. Groups of animals that had the same winning and losing track record followed by a no-fight period for 14 days were also studied. Snca mRNA levels were increased in the raphe nuclei in the losers and in the VTA of the winners. After fighting deprivation Snca mRNA levels were decreased to the control level in both groups. Snca mRNA levels were similar to the control level in the VTA of the losers and in the raphe nuclei of the winners. However Snca gene expression was increased in these areas after no-fight period in the winners and losers in comparison with respective mRNA levels in the undeprived animals. Significant positive correlations were found between the mRNA levels of Snca and Bdnf genes in the raphe nuclei. It was concluded, that social experience affects Snca gene expression depending on brain areas and functional activity of monoaminergic systems in chronically victorious or defeated mice

Anhedonia in the shadow of chronic social defeat stress, or When the experimental context matters

One of the core symptoms of major depression in human is anhedonia. For that reason, one of the main requirements towards experimental depression models is that they be able to demonstrate anhedonia in animals, that have been exposed to stressful events, and other behavioral changes attributable to a depression-like state. However, the results presented in the literature are contradictory: sweet solution intake, which is considered as a parameter of hedonic/anhedonic behavior in animals, responds quite differently to stressful situations in that it is either unaffected or increased or decreased. Different experimental designs used for the study of anhedonia in male mice exposed to chronic social defeat stress were tried to understand the reasons for so contradictory responses. Anhedonia appears as an abrupt reduction in sweet solution consumption in stressed animals and by failure to attain recovery after deprivation. However, it was also demonstrated that sucrose solution intake and preference strongly depend on the experimental context; that the possible critical factor may be prior acquaintance with the hedonic stimulus – or the lack whereof. Analysis of literature data and ours allowed us to conclude that the lack of a significant decrease in sweet solution intake in stressed animals is no evidence of lack of depression. This decrease is evidence of anhedonia only provided other symptoms of depression are present. Hedonic consumable intake can be decreased over various motivations, conditions or diseases, in particular, a high level of anxiety or pathological aggression

Down-regulation of serotonergic genes expression in the raphe nuclei of midbrain under chronic social defeat stress in male mice

Background: 
There is ample experimental evidence supporting the hypothesis that the brain serotonergic system is involved in the control of chronic social defeat stress (CSDS), depression and anxiety. The study aimed to analyze mRNA levels of the serotonergic genes in the raphe nuclei of the midbrain that may be associated with chronic social defeats consistently shown by male mice in special experimental settings. 

Methodology/Principal Findings: 
The serotonergic genes were the Tph2, Sert, Maoa and Htr1a. The Bdnf, Creb, Cphn, Gapdh, Hprt, B2M, 18S and Actb genes were also studied. The experimental groups were composed of male mice with experience of defeats in 21 daily encounters and male mice with the same track record of defeats followed by a no-defeat period without agonistic interactions (relative rest for 14 days). It has been shown that mRNA levels of the Tph2, Maoa, Sert, Htr1a, Bdnf and Creb genes in the raphe nuclei of defeated mice are decreased as compared with the controls. Under CSDS the Cphn, Gapdh, Hprt, B2M, 18S, Actb genes are also down-regulated. The expression of the serotonergic genes as well as the Cphn and Creb genes is not restored to the control level after the 2 weeks of relative rest. mRNA levels of other genes are not recovered to the control levels, although some up-regulation was observed in rested losers. Significant positive correlations were found between the total time of avoidance behavior demonstrated by the 21-day defeaters in agonistic interactions and Sert, Maoa, Bdnf, Gapdh and 18S mRNA levels. 

Conclusions: 
CSDS experience inducing the development of mixed anxious/depression-like state in male mice down-regulates the serotonergic genes expression associated with the synthesis, inactivation and reception of serotonin. The Bdnf and Creb genes as well as the cell and metabolic Cphn, Gapdh, Hprt, B2M, Actb and 18S genes in the midbrain raphe nuclei are also down-regulated under CSDS. Period of relative rest is not enough for most genes to recover expression to the control levels

Molecular Implications of Repeated Aggression: Th, Dat1, Snca and Bdnf Gene Expression in the VTA of Victorious Male Mice

Background: It is generally recognized that recurrent aggression can be the result of various psychiatric disorders. The aim of our study was to analyze the mRNA levels, in the ventral tegmental area (VTA) of the midbrain, of the genes that may possibly be associated with aggression consistently shown by male mice in special experimental settings. Methodology/Principal Findings: The genes were Th, Dat1, Snca and Bdnf; the male mice were a group of animals that had each won 20 daily encounters in succession and a group of animals that had the same winning track record followed by a no-fight period for 14 days. Increased Th, Dat1 and Snca mRNA levels were in the fresh-from-the-fight group as compared to the controls. Increased Th and Dat1 mRNA levels were in the no-fight winners as compared to the controls. Significant positive correlations were found between the level of aggression and Th and Snca mRNA levels. Conclusions: Repeated positive fighting experience enhances the expression of the Th, Dat1 and Snca genes, which ar

Th17 Cells, Glucocorticoid Resistance, and Depression

Depression is a severe mental disorder that disrupts mood and social behavior and is one of the most common neuropsychological symptoms of other somatic diseases. During the study of the disease, a number of theories were put forward (monoamine, inflammatory, vascular theories, etc.), but none of those theories fully explain the pathogenesis of the disease. Steroid resistance is a characteristic feature of depression and can affect not only brain cells but also immune cells. T-helper cells 17 type (Th17) are known for their resistance to the inhibitory effects of glucocorticoids. Unlike the inhibitory effect on other subpopulations of T-helper cells, glucocorticoids can enhance the differentiation of Th17 lymphocytes, their migration to the inflammation, and the production of IL-17A, IL-21, and IL-23 in GC-resistant disease. According to the latest data, in depression, especially the treatment-resistant type, the number of Th17 cells in the blood and the production of IL-17A is increased, which correlates with the severity of the disease. However, there is still a significant gap in knowledge regarding the exact mechanisms by which Th17 cells can influence neuroinflammation in depression. In this review, we discuss the mutual effect of glucocorticoid resistance and Th17 lymphocytes on the pathogenesis of depression