Abstract: G1 is a specific agonist of G protein-coupled estrogen receptor 30 (GPR30). However, it remains unclear whether G1 can repair the damage to hippocampal neurons and astrocytes induced by post-traumatic stress disorder (PTSD). To investigate the effects of G1 on PTSD-like behaviors and its underlying mechanisms, a PTSD mouse model was established using the single prolonged stress (SPS) method and analyzed subsequent changes in hippocampal neurons and astrocytes. The results showed that mice in the SPS model group exhibited significant PTSD-like behaviors, including anxiety, depression, and impaired fear extinction (P<0.05). Concurrently, the expressions of GPR30, glial fibrillary acidic protein (GFAP), and connexin 43 (Cx43) in the hippocampus were downregulated. Following G1 intervention, PTSD-like behaviors were significantly ameliorated (P<0.05). The expressions of GPR30, GFAP, and Cx43 were upregulated, and the number of degenerated neurons in the hippocampus was notably reduced. These findings suggest that G1 improves PTSD-like behaviors in SPS mice, and its therapeutic mechanism may be associated with the repair of hippocampal neuronal and astrocyte damage.

Key words: post-traumatic stress disorder, G protein-coupled receptor 30, neuron, astrocyte