TY - JOUR

T1 - Gene expression changes in the ventral tegmental area of male mice with alternative social behavior experience in chronic agonistic interactions

AU - Redina, Olga

AU - Babenko, Vladimir

AU - Smagin, Dmitry

AU - Kovalenko, Irina

AU - Galyamina, Anna

AU - Efimov, Vadim

AU - Kudryavtseva, Natalia

PY - 2020/9/2

Y1 - 2020/9/2

N2 - 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.

AB - 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.

KW - Chronically defeated mice (losers)

KW - Chronically winning mice (winners)

KW - Daily agonistic interactions

KW - RNA-Seq

KW - Ventral tegmental area (VTA)

KW - AGGRESSIVE-BEHAVIOR

KW - VISCERAL ENDODERM

KW - MOUSE

KW - DEPENDENT PROTEIN-KINASE

KW - CALCIUM/CALMODULIN

KW - NEUROGRANIN

KW - POSITIVE FIGHTING EXPERIENCE

KW - daily agonistic interactions

KW - chronically winning mice (winners)

KW - DEFEAT STRESS

KW - SEROTONIN

KW - LONG-TERM POTENTIATION

KW - chronically defeated mice (losers)

KW - ventral tegmental area (VTA)

UR - http://www.scopus.com/inward/record.url?scp=85090667482&partnerID=8YFLogxK

U2 - 10.3390/ijms21186599

DO - 10.3390/ijms21186599

M3 - Article

C2 - 32917038

AN - SCOPUS:85090667482

VL - 21

SP - 1

EP - 32

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 18

M1 - 6599

ER -