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Chronic stress profoundly affects mental health, significantly influencing mood, behavior, and overall quality of life. Research closely links chronic stress with mental health conditions such as depression, anxiety, and substance use disorders. Ongoing exposure to stress can lead to physiological and psychological changes, initiating a cycle of emotional distress and maladaptive coping mechanisms.
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A Rat Methyl-Seq Platform to Identify Epigenetic Changes Associated with Stress Exposure
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Genome-wide methylation patterns associated with chronic stress.

Nicholas O'Toole1,2,3, Tie-Yuan Zhang1,2,3, Eamon Fitzgerald1,2,3

  • 1Sackler Program for Epigenetics and Psychobiology, McGill University, Montréal, Canada.

Epigenomics
|January 9, 2026
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Summary
This summary is machine-generated.

Chronic social defeat stress (CSDS) alters DNA methylation in the nucleus accumbens, impacting genes linked to depression. These epigenetic changes highlight molecular pathways connecting stress to depressive disorders.

Keywords:
Social defeat stressWGBShigh throughput sequencingmethylationmouse model

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Area of Science:

  • Neuroscience
  • Epigenetics
  • Molecular Psychiatry

Background:

  • Chronic social defeat stress (CSDS) is a key animal model for depression.
  • CSDS induces lasting behavioral and brain changes, particularly in the nucleus accumbens (nAcc).

Purpose of the Study:

  • To investigate genome-wide DNA methylation patterns in the mouse nAcc after CSDS.
  • To identify epigenetic mechanisms underlying stress-induced behavioral changes.

Main Methods:

  • Genome-wide analysis of cytosine methylation in mouse nAcc following CSDS.
  • Identification and analysis of differentially methylated regions (DM regions).

Main Results:

  • CSDS led to widespread differential methylation, with increased CG hypermethylation and decreased non-CG methylation.
  • Key DM regions included genes like estrogen receptor alpha (Esr1).
  • Gene networks involving ß-catenin and Tcf4 were identified, enriched for synaptic function and estrogen-sensitive pathways.

Conclusions:

  • DNA methylation changes in the nAcc are implicated in the molecular pathways linking chronic stress to depression.
  • Significant overlap exists between DM genes in CSDS and genes associated with major depressive disorder.