Electroacupuncture alleviates depression and gastrointestinal dysfunction by rebalancing GABAergic activity in the...

Depression is frequently accompanied by gastrointestinal disturbances, reflecting the close interplay between emotional regulation and gut physiology. The central amygdala (CeA), particularly its GABAergic neurons, has been identified as a critical hub within the brain-gut axis. However, the mechanisms by which CeA inhibitory neurons mediate comorbid depressive and gastrointestinal symptoms remain poorly understood, and their potential as therapeutic targets has not been fully explored.

To investigate CeA GABAergic mechanisms linking mood and gastric function and to appraise the efficacy of electroacupuncture (EA).

A mouse model of chronic unpredictable mild stress (CUMS) was used to induce depressive-like behavior and gastric dysfunction. Behavioral tests, gastric motility assays, and fluorescent gastric emptying imaging were performed. CeA GABAergic activity was examined using immunofluorescence, calcium imaging, and chemogenetic modulation. EA was applied at CV12 and ST36 acupoints, and its therapeutic effects were evaluated across behavioral and gastric measures.

CUMS mice exhibited reduced exploration, anhedonia, increased immobility, impaired gastric motility, and delayed gastric emptying. Immunofluorescence and calcium imaging revealed hyperactivation of CeA GABAergic neurons. Chemogenetic activation reproduced depressive-like behavior and gastric dysfunction, whereas inhibition alleviated them. EA improved behavioral outcomes, restored gastric motility, and partially reversed the pathological effects of CeA overactivation. These findings demonstrate that CeA GABAergic neurons are central to the comorbidity of depression and gastrointestinal dysfunction, and that EA exerts its therapeutic effects by modulating their activity.

EA attenuates depressive-like and gastric deficits in CUMS mice, with evidence implicating CeA GABAergic neurons as a contributory node.