Effect of acupuncture on protein kinase R-like endoplasmic reticulum kinase/eukaryotic translation initiation factor 2α signaling pathway in hippocampus of rats with post-traumatic stress disorder

Abstract

To observe the effect of acupuncture on the protein kinase R-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2α (eIF2α) signaling pathway in the hippocampus of rats with post-traumatic stress disorder (PTSD), so as to explore the underlying mechanism of acupuncture in treating PTSD. Twenty-eight SD rats were randomly divided into normal, model, acupuncture and sertraline groups, with 7 rats in each group. The PTSD model was established by single prolonged stress method. The next day after modeling, acupuncture was applied to "Baihui" (GV20) and "Dazhui" (GV14) of rats in the acupuncture group for 10 min, once a day for 7 days. Sertraline (10 mg/kg) was given by gavage to rats of the sertraline group daily for 7 days. The behavioral changes of rats were detected by elevated cross maze experiment and new object recognition experiment. The expression levels of PERK,phosphorylated(p)-PERK, eIF2α, p-eIF2α and activating transcription factor 4 (ATF4) proteins in hippocampus were detected by Western blot. The ultrastructure of hippocampal neurons was observed by transmission electron microscopy. Compared with the normal group, the percentage of times and retention time of entering the open arm of the elevated cross maze experiment, and new object recognition index were significantly decreased (P<0.01); the expression levels of p-PERK, p-eIF2α and ATF4 proteins in hippocampus were significantly increased (P<0.05) of rats in the model group. Compared with the model group, the percentage of times and retention time of entering the open arm, and new object recognition index were significantly increased (P<0.05，P<0.01), the expression levels of p-PERK, p-eIF2α and ATF4 proteins in hippocampus were significantly decreased (P<0.05, P<0.01) of rats in the acupuncture and sertraline groups; the expression level of eIF2α protein was significantly decreased (P<0.05) in the sertraline group. Hippocampal neurons in the model group were damaged, the rough endoplasmic reticulum showed severe dilation, the mitochondrial cristae showed reduction or mild cavitation; compared with the model group, hippocampal neurons structural damage and the rough endoplasmic reticulum dilation were alleviated， and only some of the mitochondrial cristae decreased in the acupuncture and sertraline groups. Acupuncture can alleviate the anxiety behavior as well as the recognition and memory ability of PTSD rats, and its mechanism may be related to the inhibition of hippocampus PERK/eIF2α signaling pathway and the reduction of hippocampal neuron damage caused by endoplasmic reticulum stress.