Scalp electroacupuncture targeting trigeminal nerve activation alleviates post-traumatic stress disorder-induced depression and neuroinflammation in mice.

Scalp electroacupuncture (SA) has been clinically used as a novel treatment for ischemic stroke and depression. This study aimed to investigate whether stimulation of SA of the Baihui (GV20) and Yintang (EX-HN3) acupoints, which regulate the trigeminal nerve (TN), can alleviate depression and anxiety caused by post-traumatic stress disorder (PTSD) and to identify its therapeutic mechanism. After stimulation of SA, vasodilation and leakage within the TN area and c-Fos expression in the TN pathway of the brain were analyzed. Also, the anti-inflammatory, antidepressant, and anxiolytic effects of SA were investigated in a mouse model of PTSD induced by single prolonged stress. SA activated the TN pathway, inducing vasodilation along the TN pathway, and increased c-Fos expression in the brain, including the spinal trigeminal nucleus, locus coeruleus (LC), amygdala, and entorhinal cortex. SA significantly alleviated depression- and anxiety-related behaviors, decreased pro-inflammatory cytokines, and increased the expression of neurotrophic factors in the hippocampus. Also, SA decreased the expression of P2X7 receptors in the microglia and norepinephrine transporter in the LC and hippocampus. These results demonstrated that SA exhibited anti-inflammatory, antidepressant, and anxiolytic effects through the P2X7 receptor pathway and the LC-norepinephrine system.