HS improves hippocampal synaptic plasticity in SPS rats via PI3K/AKT signaling pathway.

Post-traumatic stress disorder (PTSD) is a severe mental illness that could impose heavy burdens on individuals and society, but effective and precise treatment modalities are unknown. The level of hydrogen sulfide (HS) in the brain plays an important role in psychiatric diseases. However, it is still unclear whether PTSD exposure could affect the level of HS and whether there is a correlation between HS levels and the pathogenesis of PTSD. In this study, we selected single prolonged stress (SPS) as a PTSD model and found that SPS exposure decreased the endogenous HS content accompanied by abnormal behavioral changes and dysregulation of the hippocampal synaptic plasticity in SPS rats. We further found that the exogenous administration of HS could alleviate PTSD-like behaviors and improve hippocampal synaptic plasticity in SPS rats. In addition, we further used the phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002 to interfere with the PI3K/AKT/BDNF signaling pathway. It was found that LY294002 significantly blocked the anti-anxiety effect and the improvement in synaptic plasticity derived from the exogenous administration of HS in SPS rats. These results suggested that the endogenous HS content was decreased in SPS rats, and that the exogenous administration of HS could ameliorate abnormal disorders and improve hippocampal synaptic plasticity by mediating the PI3K/AKT pathway.