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MANF in the Lateral Septum Dynamically Regulates Endoplasmic Reticulum Function via Transcriptomic Remodeling in Chronic Social Defeat Stress Response

ABSTRACT: This study characterized the dynamic molecular adaptations in the lateral septum (LS), a key limbic hub for stress processing, during the transition from acute to chronic social defeat stress (CSDS) in male C57BL/6J mice. Longitudinal bulk RNA-seq of LS tissue at CSDS days 1,4,7,10 revealed a biphasic endoplasmic reticulum (ER) stress response, with mesencephalic astrocyte-derived neurotrophic factor (MANF) as a core regulator. Functional validation confirmed that LS-specific MANF manipulation bidirectionally modulates ER stress, synaptic plasticity, and depressive-like behaviors in mice. Our findings identify MANF as a pivotal mediator bridging ER stress adaptation to neural circuit dysfunction in stress-induced depression.

ORGANISM(S): Mus musculus

PROVIDER: GSE326835 | GEO | 2026/06/23

REPOSITORIES: GEO

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