Aberrant Expression of Collagen Gene Family in the Brain Regions of Male Mice with Behavioral Psychopathologies Induced by Chronic Agonistic Interactions

Babenko

Kovalenko

et al. 2020

Preprint

Self Cite

There are many psychiatric medications targeting the activity of SLC transporters. Therefore, further research is needed to elucidate the expression profiles of the Slc* genes, which may serve as markers of altered brain metabolic processes and neurotransmitter activities in psychoneurological disorders. We studied differentially expressed Slc genes using the transcriptomic profiles in the ventral tegmental area (VTA), nucleus accumbens (NAcc), and prefrontal cortex (PFC) of male mice with psychosis-like behavior induced by repeated aggression experience in daily agonistic interactions which are accompanied by wins. Most of differentially expressed Slc genes in the VTA and NAcc (12 of 17 and 25 of 26, respectively) were downregulated, which was not the case in the PFC (6 and 5, up- and down, respectively). Also, the majority of these genes were shown to have brain region-specific expression profiles. In the VTA and NAcc altered expression was observed for the genes encoding the transporters of neurotransmitters as well as inorganic and organic ions, amino acids, metals, glucose, etc. This means alteration in transport functions for many substrates, which results in complete disruption of all cellular and neurotransmitter processes. The neurotransmitter systems, especially, the dopaminergic one, in male mice with positive fighting experience in daily agonistic interactions undergo changes leading to profound genomic modifications which include downregulated expression of the majority of the Slc* genes at least in the VTA and NAcc, which is attributable to chronic stimulation of the reward systems.

Section: Discussionsupporting

confidence: 56%

Reduced Expression ofSlc Genes in the VTA and NAcc of Male Mice with Positive Fighting Experience

Babenko

Kovalenko

et al. 2020

Preprint

Self Cite

“…In previous publications of our group, it was shown that stress resulting from daily agonistic interactions causes crucial changes in the expression of many genes in various brain regions of adult mice [ 5 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. Earlier, we described in detail changes in the transcription of the genes associated with the neurotransmitter systems functioning in the ventral tegmental area (VTA) of defeated male mice as compared to the controls that did not have an agonistic interaction experience [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Gene Expression Changes in the Ventral Tegmental Area of Male Mice with Alternative Social Behavior Experience in Chronic Agonistic Interactions

Redina

Babenko

et al. 2020

IJMS

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Daily agonistic interactions of mice are an effective experimental approach to elucidate the molecular mechanisms underlying the excitation of the brain neurons and the formation of alternative social behavior patterns. An RNA-Seq analysis was used to compare the ventral tegmental area (VTA) transcriptome profiles for three groups of male C57BL/6J mice: winners, a group of chronically winning mice, losers, a group of chronically defeated mice, and controls. The data obtained show that both winners and defeated mice experience stress, which however, has a more drastic effect on defeated animals causing more significant changes in the levels of gene transcription. Four genes (Nrgn, Ercc2, Otx2, and Six3) changed their VTA expression profiles in opposite directions in winners and defeated mice. It was first shown that Nrgn (neurogranin) expression was highly correlated with the expression of the genes involved in dopamine synthesis and transport (Th, Ddc, Slc6a3, and Drd2) in the VTA of defeated mice but not in winners. The obtained network of 31 coregulated genes, encoding proteins associated with nervous system development (including 24 genes associated with the generation of neurons), may be potentially useful for studying their role in the VTA dopaminergic neurons maturation under the influence of social stress.

“…However, it's necessary to take into consideration that numerous genes associated both with lithium exposure and bipolar disorder were also identified [36][37][38][39]41], and differential expression of these genes in brain tissue samples from patients and healthy controls was studied [63]: lithium exposure significantly affected 1108 genes, 702 of which were upregulated and 406 genes were downregulated. Our neurogenomic data, obtained in last years by whole transcriptomic analysis, [72,73] and collagen [74] genes specific for brain regions in mice with mixed anxiety/depression-like state. It confirms that there are many mechanisms that may account for the effects of lithium [39,75,76] on the neurochemical, cellular, and genomic levels.…”

Section: Resultsmentioning

confidence: 99%

“…However, it's necessary to take into consideration that numerous genes associated both with lithium exposure and bipolar disorder were also identified [36][37][38][39]41], and differential expression of these genes in brain tissue samples from patients and healthy controls was studied [63]: lithium exposure significantly affected 1108 genes, 702 of which were upregulated and 406 genes were downregulated. Our neurogenomic data, obtained in last years by whole transcriptomic analysis, revealed changes in the expression of mitochondrial [64], ribosomal [65,66], monoaminergic [67][68][69][70], autistic [71] genes as well as changes in the expression of neurotrophic, transcription factors [72,73] and collagen [74]…”

Section: Resultsmentioning

confidence: 99%

Effects of chronic lithium treatment on anxious behaviors and serotonergic genes expression in the midbrain raphe nuclei in defeated male mice

Kovalenko

Galyamina

et al. 2021

Preprint

Self Cite

There are experimental data that mixed anxiety/depression-like state induced by chronic social defeat stress is accompanied by development of anxiety and downregulation of serotonergic gene expression in the midbrain raphe nuclei of male mice. The paper aimed to study the effect of chronic lithium chloride (LiCl) on anxious behaviors and the expression of serotonergic genes (Tph2, Slc6a4, Htr1a, Htr5b) in the midbrain raphe nuclei of defeated mice. Slight anxiolytic effects of LiCl were found on the commucativeness in the partition test, and anxiogenic-like effects, estimated by the elevated plus-maze and social interactions tests. Chronic LiCl treatment induced overexpression of the serotonergic genes in the midbrain raphe nuclei of defeated mice. We can assume that effects of LiCl, rather anxiogenic, may be due to activation of serotonergic system induced by hyperexpression of serotonergic genes. Our findings will allow to understand the factors involved in the positive and side effects of lithium on anxiety and function of serotonergic genes which are involved into mechanisms of depression.