Neuromodulatory Effects of Alternating Current Electroacupuncture on PTSD-like Behaviors via Gut-Brain Axis Communication

<b>Background:</b> Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition with limited treatment efficacy. Alternating current electroacupuncture (AC-EA) represents a novel neuromodulatory approach, though its mechanisms-particularly its influence on the gut-brain axis-remain underexplored. <b>Methods:</b> We investigated the neurobehavioral and microbiological effects of AC-EA in a rat model of PTSD induced by single prolonged stress. Animals received AC-EA at Baihui (GV20) and Mingmen (GV4) acupoints with varying parameters (0.5 mA/20 Hz, 1 mA/20 Hz, and 1 mA/2 Hz). Behavioral tests (open field test, elevated plus maze), histopathological assessments, immunofluorescence for TLR4, and 16S rRNA sequencing of gut microbiota were performed. <b>Results:</b> AC-EA at 1 mA/2 Hz significantly improved exploratory behavior and reduced anxiety-like responses (<i>p</i> < 0.05). This regimen also restored neuronal integrity in the hippocampus and cortex and reversed PTSD-induced gut dysbiosis, enriching beneficial genera such as Ligilactobacillus. Furthermore, AC-EA downregulated hepatic TLR4 expression, indicating suppression of neuroinflammatory signaling. <b>Conclusions:</b> Our findings demonstrate that AC-EA exerts neuromodulatory and microbiota-rebalancing effects via the gut-brain axis, highlighting its potential as a non-invasive therapeutic strategy for PTSD and related brain health disorders.