Format

Send to

Choose Destination
Neuroreport. 2015 Aug 5;26(11):656-61. doi: 10.1097/WNR.0000000000000406.

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

Author information

1
Departments of aRehabilitation Medicine bOrthopedics, 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.

PMID:
26103121
DOI:
10.1097/WNR.0000000000000406
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wolters Kluwer
Loading ...
Support Center