131 M1 Microglia-Derived Exosomal Protein Stpg1 Aggravated Neuronal Ischemia/reperfusion Injury via Activating the mTOR Pathway

INTRODUCTION: The specific pathological mechanism after cerebral ischemia/reperfusion (I/R) injury remains unclear. METHODS: We used both an in vitro oxygen-glucose deprivation (OGD) model in primary neuronal culture, as well as in vivo stroke models (MCAO). Stpg1 KO mice were constructed.M1 Microglia derived exosomes (MDE) were administrated to primary neuron cells. LDH release ratio, infarct sizes were measured. Protein levels were examined by Western blot and immunofluorescence staining. RESULTS: In either direct or indirect coculture system, HT22 neuron injury was aggravated after OGD, and the growth of HT22 cells was suppressed by BV2 cells after OGD. MDE aggravated OGD injury in normal HT22 cells and wide type mice. Stpg1 was identified as the target protein that induced the hypoxic injury. The infarction size and neuronal apoptosis were less severe in Stpg1 KO mice. The upregulation of STPG1 could aggravate neuronal injury by activating the mTOR signaling pathway both in vitro and in vivo. When mTOR was knocked out, the regulatory effects of Stpg1 overexpression or knockdown against stroke disappeared. CONCLUSIONS: M1 microglia-derived exosomal protein Stpg1 could aggravate neuronal I/R injury after stroke via activating the mTOR pathway, which is a novel and pivotal cerebral ischemic injury signaling pathway and mechanism. The induction of neuronal apoptosis by the MDE Stpg1/mTOR pathway may be the potential mechanism of this protective effect.