Gene expression changes in the ventral tegmental area of male mice with alternative social behavior experience in chronic agonistic interactions

Olga Redina, Vladimir Babenko, Dmitry Smagin, Irina Kovalenko, Anna Galyamina, Vadim Efimov, Natalia Kudryavtseva

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number6599
Pages (from-to)1-32
Number of pages32
JournalInternational Journal of Molecular Sciences
Volume21
Issue number18
DOIs
Publication statusPublished - 2 Sep 2020

Keywords

  • Chronically defeated mice (losers)
  • Chronically winning mice (winners)
  • Daily agonistic interactions
  • RNA-Seq
  • Ventral tegmental area (VTA)
  • AGGRESSIVE-BEHAVIOR
  • VISCERAL ENDODERM
  • MOUSE
  • DEPENDENT PROTEIN-KINASE
  • CALCIUM/CALMODULIN
  • NEUROGRANIN
  • POSITIVE FIGHTING EXPERIENCE
  • daily agonistic interactions
  • chronically winning mice (winners)
  • DEFEAT STRESS
  • SEROTONIN
  • LONG-TERM POTENTIATION
  • chronically defeated mice (losers)
  • ventral tegmental area (VTA)

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