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Transcriptome signatures of the medial prefrontal cortex underlying GABAergic control of resilience to chronic stress exposure

ABSTRACT: To understand the mechanisms underlying resilience to chronic stress exposure observed in mice with disinhibited SST neurons (SSTCre:γ2f/f mice), we analyzed and compared the transcriptome profiles of the medial prefrontal cortex (mPFC) from male and female control (SSTCre) and mutant (SSTCre:γ2f/f) mice, with and without exposure to 21 days of chronic variable stress (CVS). We found that SSTCre:g2f/f male, but not female, mice are resilient to CVS-induced changes in the mPFC transcriptome. The CVS-induced transcriptome of stress-resilient male mice was characterized by fewer and distinct CVS-induced gene expression changes compared to the CVS-induced transcriptome of stress-vulnerable SSTCre controls. The transcriptome of non-stressed stress-resilient male mice showed stress-like transcriptome changes along with defects in signal transduction similar to stress exposed SSTCre stress-vulnerable controls. These features of non-stressed stress-resilient mice were normalized by chronic stress exposure, along with enhancement of mRNA translation. Stress-induced differentially expressed genes of stress-vulnerable, but not stress-resilient mice were prominently associated with risk genes of human stress-related psychiatric disorders.

ORGANISM(S): Mus musculus

PROVIDER: GSE272496 | GEO | 2024/11/05

REPOSITORIES: GEO

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