A central CeA-LC-PVH circuit mediates stress-induced osteopenia via skeletal sympathetic nerves in male mice.

ABSTRACT: Chronic stress disrupts skeletal homeostasis, yet central neural mechanisms remain unclear. In this study, we demonstrated that hyperactivation of locus coeruleus noradrenergic (LC^NE+) neurons was both necessary and sufficient to drive bone loss in a mouse model of chronic social defeat stress (CSDS). Mechanistically, CSDS induced a bidirectional imbalance in the central amygdala corticotropin-releasing hormone (CRH)-expressing (CeA^CRH+) neurons to LC^NE+ circuit, characterized by enhanced CRH release and suppressed GABAergic transmission. A CeA^CRH+-LC^NE+-paraventricular hypothalamic CRH-expressing (PVH^CRH+) pathway was identified, which propagated stress signals to bone via sympathetic outflows. These findings redefine centr

SUBMITTER: Zhao WJ 

PROVIDER: S-EPMC12680053 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature