Electroacupuncture attenuates anxiety caused by chronic mild stress through inhibiting NOX2-derived oxidative stress in ventral hippocampus

Anxiety disorders are highly prevalent and often triggered or worsened by chronic stress, yet current pharmacological treatments have limitations. Electroacupuncture (EA), a modern adaptation of traditional acupuncture, has shown promise as an alternative therapy for anxiety, though its mechanisms remain unclear. In this study, we investigated whether EA can alleviate anxiety-like behaviors induced by chronic mild stress (CMS) in mice, focusing on the role of NOX2-mediated oxidative stress and synaptic function in the ventral hippocampus. CMS exposure led to increased anxiety-like behavior, enhanced excitatory synaptic transmission, and elevated oxidative stress specifically in the ventral CA1 (vCA1) region. EA treatment was associated with normalization of excitatory/inhibitory synaptic balance and reduction in oxidative stress markers and NOX2 expression. Furthermore, overexpression of NOX2 in vCA1 induced anxiety-like behaviors, which EA partially ameliorated. These findings suggest that EA's anxiolytic effects may involve NOX2-related oxidative stress pathways and hippocampal excitability modulation, providing mechanistic insights that warrant further investigation for potential therapeutic applications (Graphical Abstract).