Elevated neuronal α-synuclein promotes microglia activation after spinal cord ischemic/reperfused injury

The present study aimed to investigate the mechanism of injured neurons caused by ischemia/reperfusion in the induction of microglia activation. Spinal neurons were prepared and exposed to ischemic/reperfused conditions. The -synuclein protein levels in these cells were analyzed by western blot, immunofluorescence, or enzyme-linked immunosorbent assay. Ischemia/reperfusion exposure led to elevated -synuclein protein expression and release. Furthermore, when cocultured with injured neurons or supernatants from injured neurons, nitric oxide generation, H2O2 production, and tumor necrosis factor- expression were promoted in microglia. Nevertheless, this effect was impeded by pretreatment of the -synuclein antibody in the supernatants from injured neurons. Moreover, toll-like receptor 2 (TLR2) rather than TLR3 or TLR4 mediated microglia activation by -synuclein. This process involved p38 MAPK and NF-B activation, the inhibition of which resulted in reduced NADPH oxidase 2 (Nox2) in microglia. In conclusion, ischemia/reperfusion-injured neurons could express and release increased levels of -synuclein and cause microglia activation through TLR2 both in vitro and in vivo. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.