1. Academic Validation
  2. Electroacupuncture alleviates depression and gastrointestinal dysfunction by rebalancing GABAergic activity in the central amygdala

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

  • World J Psychiatry. 2026 Feb 19;16(2):114736. doi: 10.5498/wjp.v16.i2.114736.
Hong-Kun Ma 1 2 Shan-Lan Zhu 3 Xue-Yan Li 3 Yi Yuan 4 Qing-Yang Huang 3 Hao Wang 3 Guo-Ming Shen 3 5 Xi-Yang Wang 6
Affiliations

Affiliations

  • 1 College of Acupuncture and Moxibustion, Anhui University of Chinese Medicine, Hefei 230012, Anhui Province, China.
  • 2 Anhui Province Key Laboratory of Meridian Viscera Correlationship, Anhui University of Chinese Medicine, Hefei 230012, Anhui Province, China.
  • 3 College of Integrated Chinese and Western Medicine (School of Life Science), Anhui University of Chinese Medicine, Hefei 230012, Anhui Province, China.
  • 4 School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
  • 5 Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei 230061, Anhui Province, China.
  • 6 College of Integrated Chinese and Western Medicine (School of Life Science), Anhui University of Chinese Medicine, Hefei 230012, Anhui Province, China. [email protected].
Abstract

Background: 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.

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

Methods: 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.

Results: 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.

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

Keywords

Central amygdala; Chronic stress; Depression; Electroacupuncture; GABAergic neurons; Gastrointestinal motility; Gut-brain axis.

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