NeuroReport. 26(11):656–661, AUGUST 5TH, 2015
DOI: 10.1097/WNR.0000000000000406
,
PMID: 26103121
Issn Print: 0959-4965
Publication Date: August 5th, 2015
Elevated neuronal α-synuclein promotes microglia activation after spinal cord ischemic/reperfused injury
Hongfei Qiao;Qiaojun Zhang;Haifeng Yuan;Yali Li;Dong Wang;Rui Wang;Xijing He;
+ Author Information
Departments of aRehabilitation MedicinebOrthopedics, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
Abstract
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 α-synuclein protein levels in these cells were analyzed by western blot, immunofluorescence, or enzyme-linked immunosorbent assay. Ischemia/reperfusion exposure led to elevated α-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-α expression were promoted in microglia. Nevertheless, this effect was impeded by pretreatment of the α-synuclein antibody in the supernatants from injured neurons. Moreover, toll-like receptor 2 (TLR2) rather than TLR3 or TLR4 mediated microglia activation by α-synuclein. This process involved p38 MAPK and NF-κB 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 α-synuclein and cause microglia activation through TLR2 both in vitro and in vivo.
