Electroacupuncture at “Siguan” acupoints alleviates post-stroke depression by inhibiting ER stress-induced apoptosis in the prefrontal cortex

This study investigated the complex mechanisms underlying post-stroke depression (PSD) and the challenges associated with its clinical prevention and treatment. Specifically, it examined the effects of electroacupuncture at the “Siguan” acupoints on PSD and the relationship with the PERK-ATF4-CHOP endoplasmic reticulum stress (ERS) pathway. A rat model of PSD was established by combining middle cerebral artery occlusion (MCAO) with solitary rearing and chronic unpredictable mild stress (CUMS). Successfully modeled rats were randomly assigned to four groups: the model group, the electroacupuncture group, the drug group, and the sham operation group. The electroacupuncture group received 21 days of electroacupuncture at the “Siguan” acupoints (bilateral Hegu LI4 and Taichong LR3). Behavioral changes were assessed using a blinded method. Histopathological and molecular biological methods were then employed to comprehensively examine neuronal damage, apoptosis, and the expression of key proteins in the ERS pathway in the prefrontal cortex. The results showed that, compared with the model group, both electroacupuncture and medication significantly improved depressive‑like behavior, alleviated neuronal injury in the prefrontal cortex, and reduced apoptosis. At the molecular level, these effects were significantly associated with inhibition of the PERK-ATF4-CHOP ERS pathway, as evidenced by decreased levels of GRP78, p-PERK, CHOP, and downstream pro‑apoptotic proteins (Bax and cleaved caspase‑3). Notably, electroacupuncture demonstrated particular efficacy in promoting weight gain and modulating pathways such as p-PERK. These findings suggest that electroacupuncture at the “Siguan” acupoints may alleviate depressive‑like behavior in PSD rats by inhibiting the PERK-ATF4-CHOP pathway in the prefrontal cortex, thereby reducing endoplasmic reticulum stress‑induced neuronal apoptosis. This provides a novel potential molecular mechanism for electroacupuncture treatment of PSD.