Gypenoside XVII regulates apoptosis and fear extinction deficits mediated by post-traumatic stress disorder through the PERK/CHOP signaling pathway.

OBJECTIVE

Post-traumatic stress disorder (PTSD) leads to apoptosis in the medial prefrontal cortex (mPFC). Although studies have demonstrated the neuroprotective effects of Gypenoside XVII(GP-17), the potential mechanisms of GP-17 for the treatment of PTSD remain to be elucidated. This study aimed to investigate the inhibitory effect of GP-17 on the fear state of PTSD through the PERK/CHOP pathway.

MATERIALS AND

METHODS

Establishment of a Single Prolonged Stress (SPS) model using Sprague Dawley (SD) rats, combined with behavioral assessments, TUNEL staining, Western blot analysis, Immunofluorescence staining, and Flow cytometry analyses of a primary microglia model. This study aims to evaluate the effects of GP-17 treatment on fear and anxiety states, as well as the role of the endoplasmic reticulum (ER) stress signaling pathway, specifically protein kinase RNA (PKR)-like ER kinase (PERK), in regulating apoptosis in rats.

RESULTS

Research shows that GP-17 significantly reduces apoptosis in the prefrontal cortical microglia of SPS rats by modulating the PERK-C/EBP-homologous protein (CHOP) signaling pathway. This modulation helps improve fear extinction deficits and reduces anxiety-like behavior. Additionally, GP-17 intervention effectively inhibits neuroinflammation and oxidative stress. In vitro experiments further demonstrate that GP-17 prevents tunicamycin (Tu)-induced apoptosis related to PERK-mediated ER stress in primary rat microglia.

CONCLUSION

GP-17 demonstrates therapeutic potential for PTSD by modulating fear and anxiety in SPS rats through the PERK/CHOP pathway, positioning it as a promising candidate for PTSD treatment via the endoplasmic reticulum stress pathway.