Activation of glial α7 nAChR promotes neurogenesis by suppressing Aβ-mediated neuroinflammation in Alzheimer's disease

Here, we report the effects of glial cells alpha 7 nicotinic acetylcholine receptor (alpha 7-nAChR) activation on neuroinflammation and proliferation as well as on the differentiation of implanted neural stem cells (NSCs). It was observed that nicotine reduced the levels of inflammatory mediators in the glial cell and NSCs co-culture system, and the rate of NSCs apoptosis demonstrated a comparable decline. In addition, both the in vitro and the in vivo study showed that nicotine amplified the proliferation of NSCs, and the neuronal and cholinergic neuronal differentiation of NSCs increased significantly, supplementing the nerve cells of the central nervous system. The anti-inflammatory and nerve regeneration-promoting effect of nicotine was reversed upon treatment with a-bungarotoxin, an inhibitor of a7-nAChR. These results suggest that, activation of a7-nAChR on glial cells attenuates the effects of neuroinflammation on the proliferation and differentiation of NSCs by reducing the secretion of inflammatory factors. In conclusion, the promotion of neurogenesis and simultaneous reduction of neuroinflammation is a promising strategy for therapy in Alzheimer's disease.