Electroacupuncture Ameliorates Alcohol-Related Cognitive Impairment by Modulating the Gut-Brain Axis to Alleviate LPS Driven Neuroinflammation.

OBJECTIVE

To investigate whether electroacupuncture (EA) at Zusanli (ST36) ameliorates alcohol-related cognitive impairment (ARCI) by restoring intestinal barrier integrity and to elucidate the role of the vagus nerve in this "gut-to-brain" protective mechanism.

METHODS

An ARCI mouse model was established by daily ethanol gavage for 28 days. Mice received EA at ST36 from day 15 onwards. Behavioral tests (MWM, OFT, EPM) were conducted to assess cognitive and emotional function. Time-course analysis of intestinal pathology (H&E, ZO-1), permeability (FITC-LPS, DAO), and neuroinflammation (LPS, IBA-1, cytokines) was performed. The role of the vagus nerve was investigated using ipsilateral DMV lesion and exogenous LPS challenge.

RESULTS

Chronic alcohol exposure caused significant cognitive deficits, anxiety-like behaviors, and body weight loss, accompanied by early-onset intestinal barrier disruption and elevated LPS, which preceded central neuroinflammation. EA at ST36 significantly ameliorated these behavioral and pathological changes. EA activated DMV cholinergic neurons, restored ZO-1 expression, and reduced LPS translocation. Crucially, both DMV lesion and exogenous LPS administration abolished EA's protective effects on the intestinal barrier, neuroinflammation, and behavior.

CONCLUSION

EA at ST36 alleviates ARCI by activating the vagus nerve to restore intestinal barrier integrity, thereby preventing gut-derived LPS from triggering neuroinflammation. This identifies a key vagal-dependent mechanism and supports EA as a promising intervention for ARCI.