Chronic social defeat stress differentially regulates the expression of BDNF transcripts and epigenetic modifying enzymes in susceptible and resilient mice

World J Biol Psychiatry. 2019 Sep;20(7):555-566. doi: 10.1080/15622975.2018.1500029. Epub 2018 Sep 19.

Abstract

Objectives: Although stress is considered a primary risk factor for neuropsychiatric disorders, a majority of individuals are resilient to the effects of stress exposure and successfully adapt to adverse life events, while others, the so-called susceptible individuals, may have problems to properly adapt to environmental changes. However, the mechanisms underlying these different responses to stress exposure are poorly understood.Methods: Adult male C57BL/6J mice were exposed to chronic social defeat stress protocol and levels of brain derived neurotrophic factor (BDNF) transcripts and epigenetic modifying enzymes were analysed by real-time PCR in the hippocampus (HPC) and prefrontal cortex (PFC) of susceptible and resilient mice.Results: We found a selective reduction of BDNF-6 transcript in the HPC and an increase of BDNF-4 transcript in the PFC of susceptible mice. Moreover, susceptible mice showed a selective reduction of the g9a mRNA levels in the HPC, while HDAC-5 and DNMT3a mRNA levels were specifically reduced in the PFC.Conclusions: Overall, our results, showing a different expression of BDNF transcripts and epigenetic modifying enzymes in susceptible and resilient mice, suggest that stress resilience is not simply a lack of activation of stress-related pathways, but is related to the activation of additional different specific mechanisms.

Keywords: Stress; epigenetic; hippocampus; histone-modifying enzymes; prefrontal cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Psychological
  • Animals
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA Methyltransferase 3A
  • Disease Susceptibility
  • Epigenesis, Genetic
  • Hippocampus / enzymology*
  • Histone Deacetylases / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Prefrontal Cortex / enzymology*
  • Stress, Psychological / enzymology*
  • Stress, Psychological / genetics

Substances

  • Bdnf protein, mouse
  • Brain-Derived Neurotrophic Factor
  • Dnmt3a protein, mouse
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • Hdac5 protein, mouse
  • Histone Deacetylases