Abstract
Functional lateralization of the prefrontal cortex has been implicated in stress and emotional disorders, yet underlying gene expression changes remains unknown. Here, we report molecular signatures lateralized by chronic social defeats between the two medial prefrontal cortices (mPFCs). Stressed mice show 526 asymmetrically expressed genes between the mPFCs. This cortical asymmetry selectively occurs in stressed mice with depressed social activity, but not in resilient mice with normal behavior. We have isolated highly asymmetric genes including connective tissue growth factor (CTGF), a molecule that modulates wound healing at the periphery. Knockdown of CTGF gene in the right mPFC by shRNA led to a stress-resistant behavioral phenotype. Overexpression of CTGF in the right mPFC using viral transduction induces social avoidance while the left mPFC thereof prevent stress-induced social avoidance. Our study provides a molecular window into the mechanism of stress-induced socioemotional disorders, which can pave the way for new interventions by targeting cortical asymmetry.
Highlights
stressed mice (Stress) induces numerous physiological changes in the brain, but only some individuals develop emotional disorders
Chronic social defeat stress induces asymmetric gene expression in the medial prefrontal cortices (mPFCs) To determine whether stress induces gene expression asymmetry in the mPFC, we performed chronic social defeat experiments using C57BL/6 J mice, as previously described [17] (Fig. 1a)
Our study reveals that chronic social defeat stress induces hemisphere-specific gene expression in the mPFC, opening a new avenue for studying the molecular mechanisms of hemispheric lateralization and stress-induced mental illness (Fig. 6)
Summary
Stress induces numerous physiological changes in the brain, but only some individuals develop emotional disorders. Studies have sought to identify key mechanisms and molecules that explain the relationship between stress and emotional disorders. Brain imaging studies have revealed that patients with post-traumatic stress disorder (PTSD) [1, 2] or depression [3,4,5] show asymmetric activity between the two prefrontal cortices (PFC). Chronic social defeat stress depresses activity in the left mPFC but not the right mPFC; consistent with this, optogenetic stimulation of activity in the depressed left mPFC, but not the depressed right mPFC, restores stressinduced social avoidance, which is a pro-resilience effect [9]. Despite the data derived from these lesion and gainof-function studies, the physiological mechanisms and related molecular markers associated with stress-induced emotional changes remain unclear
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