Electroacupuncture Alleviates Neuroinflammation and Memory Dysfunction by Regulating Hippocampal Microglial α7nAChR in LPS-Induced Systemic Inflammation in Mice

Abstract

Background Cognitive impairment induced by systemic inflammatory diseases is associated with hippocampal microglial activation and central neuroinflammation. This paper investigated whether electroacupuncture (EA) stimulation exerts anti-inflammatory effects and improves cognitive impairment through the hippocampal microglial α7 receptor. Methods ES efficacy was evaluated with respect to microglial activation and cognitive dysfunction amelioration following lipopolysaccharide (LPS) intraperitoneal injection in mice. Behavioral testing of “what,” “where,” and “when” memories was used to observe spatial memory. Microglial α7 was knocked out by hybridization of α7nAchR^fl/fl and Cx3Cr1^cre transgenic mice. Furthermore, the cholinergic transmission between medium septum (MS) and the hippocampus (HP) was studied using magnetic resonance spectroscopy to investigate the EA effects on the central cholinergic anti-inflammatory properties. Results EA can improve the spatial memory and increase the cholinergic level of the MS and promote the cholinergic transmission of MS–HP. EA also activated the cholinergic neurons of MS, increased the expression of microglial α7nAChR, and decreased the expression of Iba-1. The results of qPCR and enzyme-linked immunosorbent assay detection showed EA could reduce the expression of mRNA related to cytokine (IL-1β, iNOS, IL-10, Arg1, CD206, and TNF-α) in the HP. Hippocampal injection of a7 antagonist or specific knockout of microglia a7 can reverse the EA effects of anti-inflammatory properties and improve cognitive impairment. Conclusion EA treatment ameliorates system inflammation-induced cognitive decline mediated by hippocampal microglial α7 receptor, which displays cholinergic antineuroinflammation properties and improves cognitive function.