Identification of genes and pathways associated with chronic restraint stress-induced anxiodepressive-like behaviors in female mice by transcriptomic and genome-wide DNA methylation combinational-analysis
Preclinical study reveals stress-induced DNA hypermethylation and altered gene expression in female mice, highlighting epigenetic mechanisms behind sex-specific depressive behaviors.
Key Points
To identify the transcriptomic and genome-wide DNA methylation alterations in the medial prefrontal cortex associated with chronic stress-induced anxiety and depression in females.
Exposed female mice to chronic restraint stress (CRS) for two weeks to induce anxiodepressive-like behaviors.
Isolated medial prefrontal cortex (mPFC) tissue and conducted RNA sequencing (RNA-Seq) along with whole-genome enzymatic methylation sequencing (EM-seq).
Identified 105 upregulated genes (primarily involved in complement and coagulation cascades) and 71 downregulated genes (including neurotransmitter receptors and neuronal activity markers) following CRS.
Detected 6,848 hypermethylated and 4,530 hypomethylated genomic regions across both CG and CHH contexts in the mPFC.
Integrated analysis revealed 13 downregulated genes with significant hypermethylation linked to neuronal activity regulation, along with 8 hypomethylated upregulated genes.