Social defeat stress in adult mice causes alterations in gene expression, alternative splicing, and the epigenetic landscape of H3K4me3 in the prefrontal cortex: An impact of early-life stress

V. V. Reshetnikov, P. E. Kisaretova, N. I. Ershov, T. I. Merkulova, N. P. Bondar

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Chronic stress is the leading risk factor of a broad range of severe psychopathologies. Nonetheless, the molecular mechanisms triggering these pathological processes are not well understood. In our study, we investigated the effects of 15-day social defeat stress (SDS) on the genome-wide landscape of trimethylation at the 4th lysine residue of histone H3 (H3K4me3) and on the transcriptome in the prefrontal cortex of mice that were reared normally (group SDS) or subjected to maternal separation early in life (group MS+SDS). The mice with the history of stress early in life showed increased susceptibility to SDS in adulthood and demonstrated long-lasting genome-wide alterations in gene expression and splicing as well as in the H3K4me3 epigenetic landscape in the prefrontal cortex. Thus, the high-throughput techniques applied here allowed us to simultaneously detect, for the first time, genome-wide epigenetic and transcriptional changes in the murine prefrontal cortex that are associated with both chronic SDS and increased susceptibility to this stressor.

Original languageEnglish
Article number110068
Number of pages16
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume106
Early online date15 Aug 2020
DOIs
Publication statusPublished - 2 Mar 2021

Keywords

  • Alternative splicing
  • Early-life stress
  • H3K4me3
  • RNA-seq
  • Social defeat stress
  • CHILDHOOD MALTREATMENT
  • DEPRESSION
  • MATRIX GLA PROTEIN
  • RESILIENCE
  • TRANSCRIPTION
  • DISTINCT
  • MECHANISMS
  • NUCLEUS-ACCUMBENS
  • MOLECULAR ADAPTATIONS
  • PSYCHIATRIC-DISORDERS

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