Social Behaviour and Epigenetic Status in Adolescent and Adult Rats: The Contribution of Early-Life Stressful Social Experience

Cell Mol Neurobiol. 2019 Apr;39(3):371-385. doi: 10.1007/s10571-019-00655-x. Epub 2019 Feb 1.

Abstract

Early-life experiences have been linked to individual's epigenetic status and social behaviour. Therefore, the present study aims to test whether the presence of mother suppress the early-life stressful social experience (SSE)-induced effect on social behaviour of adolescent and adult rats, and associated epigenetic changes. To test this, experimental groups [maternally separated pups (MSP)/pups with their mother (M+P)] were allowed to experience the presence of a stranger (ST), and then their social behaviour was compared with the maternal separated (MS) and control (Con) group. We observed that MS, MSP-ST group showed less social interaction with the unknown conspecifics than known conspecifics compared to other groups. Subsequently, we found that SSE elevated the level of DNA methyltransferases (Dnmt3a), ten-eleven translocation (Tet3), methyl-CpG-binding protein-2 (MeCP2) and Repressor Element-1 Silencing Transcription Factor (REST) in amygdala of adolescent and adult MS, MSP-ST groups compared to other groups. As expected, SSE altered the histone (H3) lysine (K14/K9) acetylation (ac) and H3K4/K9 methylation (me2/me3). SSE decreased the level of H3K14ac and H3K9ac in adolescents and then increased in adults. Interestingly, H3K4me2/me3 levels were elevated in adolescent and adults. Whereas H3K9me2/me3 shows contrasting pattern in adolescent, but H3K9me2/me3 levels were increased in adults. In addition, the expression of brain-derived neurotrophic factor (BDNF) was reduced in MS, MSP-ST groups' adolescent and adult rats. Observed correlation between epigenetic changes and social behaviour possibly contributed by early-life SSE in the absence of mother, but mother's presence suppresses the effect of early-life SSE.

Keywords: Amygdala; Early-life stress; Epigenetics; Histone acetylation; Histone methylation; Social behaviour.

MeSH terms

  • Acetylation
  • Aging / genetics*
  • Amygdala / metabolism
  • Animals
  • Behavior, Animal
  • Brain-Derived Neurotrophic Factor / metabolism
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methyltransferase 3A
  • Dioxygenases / metabolism
  • Epigenesis, Genetic*
  • Female
  • Histones / metabolism
  • Interpersonal Relations
  • Methyl-CpG-Binding Protein 2 / metabolism
  • Methylation
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Wistar
  • Repressor Proteins / metabolism
  • Social Behavior*
  • Stress, Psychological / genetics*

Substances

  • Brain-Derived Neurotrophic Factor
  • Histones
  • Methyl-CpG-Binding Protein 2
  • RE1-silencing transcription factor
  • RNA, Messenger
  • Repressor Proteins
  • Dioxygenases
  • Tet3 protein, rat
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A