FGF2 alleviates PTSD symptoms in rats by restoring GLAST function in astrocytes via the JAK/STAT pathway.

In our previous study, we demonstrated that fibroblast growth factor 2 (FGF2) administration alleviated posttraumatic stress disorder (PTSD) symptoms via an "astrocyte-related" mechanism. We further investigated the changes in the astrocytic glutamate transporters GLAST and GLT-1 and in JAK/STAT3 signaling (which is involved in astrocyte activation and GLAST/GLT-1 function) in single prolonged stress (SPS) model rats. High-performance liquid chromatography (HPLC), Western blot and immunohistochemistry analyses revealed a significant SPS-induced increase in the concentration of glutamate in the cerebrospinal fluid and decrease in GLAST/GLT-1 expression and JAK/STAT3 signaling. Treatment with FGF2 significantly alleviated GLAST/GLT-1 dysfunction, JAK/STAT3 signaling inhibition, and the behavioral abnormalities. The administration of the JAK/STAT pathway inhibitor AG490 blocked the effects of FGF2 on PTSD symptoms, astrocyte activation, and GLAST, but not GLT-1, expression in vivo and in vitro. Our findings suggest that astrocytic JAK/STAT signaling is associated with SPS-induced GLAST dysfunction and that FGF2 protects against PTSD symptoms by restoring astrocytic glutamate uptake via the JAK/STAT signaling pathway.