[Altered Expression of Neurotransmitters Systems' Genes in the Ventral Tegmental Area of Depressive Male Mice: Data of RNA-Seq]

Zh Vyssh Nerv Deiat Im I P Pavlova. 2017 Jan;67(1):113-128.
[Article in Russian]

Abstract

Chronic social defeat stress (CSDS) leads to the development of mixed anxiety/depression-like state in male mice similar to those in humans. It has been shown that, under CSDS, the adult brain undergoes changes in the functioning neurotransmitter systems in different brain regions. In this experiment we are focused on the analysis of expression of genes encoding proteins related with the metabolism and receptors of serotonin, catecholamines, GABA and glutamate in the ventral teg- mental area which is important for regulation of motivations, emotions and is involved into mech- anisms of affective disorders. Mixed anxiety/depression-like state was generated in male mice by exposure to CSDS during 20 days. The collected samples of the ventral tegmental area were se-- quenced at JSC Genoanalytica,(http://genoanalytica.ru/, Moscow, Russia).'We found that genes, related with serotonin (Tph2, Maob, SIc6a4, Htr4, Htr1a) were upregulated but expression of Htr3a gene was downregulated in the ventral tegmental area of depressive mice in comparison with the control. Besides, upregulation of dopaminergic Th, Ddc, Slc6a3, Sic18a2, Drd2, and Maob genes was found while noradrenergic Dbh, Slc6a2, Adra2c, and Adra2a genes were downregulated. Ex- pression of GABAergic Gabral, Gabra2, Gabrg2, Gabrg], Gabrq, Gad], and Gad genes as well as glutamatergic Grial, Gria2, Grik2, Grm2, Grm5, and Slc 7a8 genes were increased under CSDS. Development of mixed anxiety/depression-like state under CSDS in male mice is accompanied by increased expression of genes coding the proteins participating in the metabolism and receptions of serotonergic, dopaminergic, glutamatergic and GABAergic systems. Expression of genes coding the adrenergic reception is decreased. It is supposed that Drd2 H Htr3a genes may play the key role in the synchronization of other genes of neurotransmitter systems.

MeSH terms

  • Animals
  • Anxiety / genetics*
  • Anxiety / metabolism
  • Anxiety / physiopathology
  • Depression / genetics*
  • Depression / metabolism
  • Depression / physiopathology
  • Disease Models, Animal
  • Dominance-Subordination
  • Dopamine / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Glutamic Acid / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / classification
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Neurotransmitter Agents / metabolism*
  • Serotonin / metabolism
  • Stress, Psychological / genetics*
  • Stress, Psychological / metabolism
  • Stress, Psychological / physiopathology
  • Synaptic Transmission
  • Ventral Tegmental Area / metabolism*
  • Ventral Tegmental Area / physiopathology
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Nerve Tissue Proteins
  • Neurotransmitter Agents
  • Serotonin
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Dopamine