Deletion of p75NTR rescues behavioral and cognitive dysfunction in SPS-induced PTSD mice through hippocampal PI3K/Akt/mTOR pathway.

Post-traumatic stress disorder (PTSD) is a persistent mental illness caused by severe traumatic events, and its pathogenesis is still unclear. Recent studies indicate that p75 neurotrophic factor receptor (p75NTR) plays a crucial role in neurological diseases, but the role of p75NTR in PTSD is currently unknown. To investigate the effects and mechanisms of p75NTR in PTSD, in this study, a functional p75NTR-deficient mouse was used to establish a PTSD model by single prolonged stress (SPS) paradigm, then the behavioral effects and underlying mechanisms were further investigated. The results demonstrated that p75NTR deletion alleviated anxiety-like behavior and spatial learning and memory impairment in SPS-induced PTSD mice. Further study indicated that deletion of p75NTR downregulated the expression of apoptosis (Bax) and autophagy (Beclin-1) related proteins in the hippocampus of PTSD mice, protected against hippocampal neuronal damage, upregulated the expression of synaptic-related proteins (PSD95 and Synapsin I), increased dendritic complexity and dendritic spine density, and improved synaptic plasticity through the PI3K/Akt/mTOR pathway. In conclusion, deletion of p75NTR rescues behavioral and cognitive dysfunction through PI3K/Akt/mTOR pathway mediated regulation of hippocampal autophagy, apoptosis and synaptic plasticity in SPS-induced PTSD mice, which provides a potential therapeutic target for the treatment of PTSD.