Α‐synuclein induces microglial cell migration through stimulating HIF‐1α accumulation

Microglial cell migration and infiltration plays a critical role in spinal cord injury after thoracoabdominal aortic surgery. In our previous study, α‐synuclein, a presynaptic protein was shown to be released from injured neurons and cause microglial cell activation. Here, we aimed to explore the effect of α‐synuclein on microglial cell migration. Primary microglial cells were isolated from Sprague–Dawley rats and then exposed different doses (0.2, 0.4, and 0.6 μM) of α‐synuclein oligomers. The mRNA and protein levels of HIF‐1α were then analyzed by qRT‐PCR and Western blot. Cell migration was examined by a 96‐well Boyden chamber. Moreover, toll‐like receptor (TLR) 2‐expression as well as TLR7/8‐expression was inhibited by specific siRNA transfection. HIF‐1α was overexpressed by Ad‐HIF‐1α transfection. In the results, α‐synuclein was found to stimulate HIF‐1α accumulation in microglial cells in a dose‐dependent manner. Silencing HIF‐1α expression dampened α‐synuclein induced microglial cell migration. Furthermore, blockade of TLR7/8 expression but not TLR2 expression reduced HIF‐1α accumulation in microglial cells. In addition, overexpressed HIF‐1α, along with Src, prompted caveolin‐1 expression and phosphorylation, as well as migration in microglial cells. Α‐synuclein acts via TLR7/8 and enhances HIF‐1α expression, which might play a regulatory role in microglial cell migration. © 2017 Wiley Periodicals, Inc.