Molecular laterality encodes stress susceptibility in the medial prefrontal cortex

• Published in: Molecular brain Vol. 14; no. 1; pp. 92 - 17
• Main Authors: Chae, Sujin, Hong, Jiso, Kang, Keunsoo, Shin, Anna, Kim, Dae-Gun, Lee, Sinjeong, Kim, Moo-young, Jung, Inkyung, Kim, Daesoo
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 14.06.2021; BioMed Central; BMC
• Subjects: Adaptation; Animals; Asymmetry; Avoidance Learning; Brain; Camcorders; Chronic Disease; Connective tissue growth factor; Connective tissue growth factor (CTGF); Connective Tissue Growth Factor - genetics; Connective Tissue Growth Factor - metabolism; Connective tissues; Depression; Depression, Mental; Disease Susceptibility; Emotional disorders; Ethylenediaminetetraacetic acid; Gene expression; Gene Expression Regulation; Genes; Hemispheric laterality; Male; Medial prefrontal cortex; Mice; Mice, Inbred C57BL; Models, Biological; Molecular laterality; Molecular Sequence Annotation; Phenotypes; Physiology; Post traumatic stress disorder; Prefrontal cortex; Prefrontal Cortex - pathology; Resilience, Psychological; Social behavior; Social Defeat; Social defeat stress; Social interaction; Social interactions; Stress (Psychology); Stress, Psychological - genetics; Stress, Psychological - pathology; Sucrose; Wound healing; United States > US; Connective tissue growth factor (CTGF); Medial prefrontal cortex; Social defeat stress; Depression; Molecular laterality
• ISSN: 1756-6606; 1756-6606
• DOI: 10.1186/s13041-021-00802-w

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.