IMR Press / JIN / Volume 18 / Issue 1 / DOI: 10.31083/j.jin.2019.01.114
Open Access Original Research
Acetylcholine suppresses microglial inflammatory response via α7nAChR to protect hippocampal neurons
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1 Department of Physiology, School of Medicine, and Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu Province 226001, China
*Correspondence: yppeng@ntu.edu.cn (Yu-Ping Peng); yhqiu@ntu.edu.cn (Yi-Hua Qiu)
# These two authors contributed equally to the study.
J. Integr. Neurosci. 2019, 18(1), 51–56; https://doi.org/10.31083/j.jin.2019.01.114
Submitted: 6 December 2018 | Accepted: 22 March 2019 | Published: 30 March 2019
Copyright: © 2019 Li et al. Published by IMR press.
This is an open access article under the CC BY-NC 4.0 license (https://creativecommons.org/licenses/by-nc/4.0/)
Abstract

Neuroinflammation is principally linked to glial function and has been demonstrated to participate in the pathogenesis of Alzheimer's disease, a neurodegenerative disorder characterized by beta-amyloid ccumulation and neurotransmission disruption. Previous findings suggest acetylcholine exerts anti-inflammatory and neuroprotective properties in several neurodegenerative disorders. However, the underlying mechanisms remain elusive. Here evaluation of the influence of acetylcholine on neuroinflammation and neurodegeneration in Alzheimer's disease is reported and further neuroprotective mechanisms are investigated. Investigation of microglia in lipopolysaccharide-induced hippocampal neuronal toxicity employed $\alpha$7nAChR gene silencing and demonstrated that both the anti-inflammatory and neuroprotective effects of acetylcholine rely on $\alpha$7nAChR pathways. As expected, in neuron-microglia co-cultures lipopolysaccharide induced an increase in expression of pro-inflammatory factors, including inducible nitric oxide synthase, interleukin-1$\beta$, and tumor necrosis factor-$\alpha$, and decreased expression of neurotrophic factors such as insulin-like growth factor-1, and neuronal apoptosis. Acetylcholine protects against lipopolysaccharide-elicited neuronal injury by inhibiting the microglial inflammatory response and promoting microglial neurotrophic factor production via the action of $\alpha$7nAChR on microglia. These findings establish that ACh activates $\alpha$7nAChR in microglia, which in turn protects hippocampal neurons.

Keywords
Acetylcholine
α7nAChR
hippocampal neuron
lipopolysaccharide
microglia
Figures
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