title: Huperzine A protects sepsis associated encephalopathy by promoting the deficient cholinergic nervous function.
abstract: Neuroinflammatory deregulation in the brain plays a crucial role in the pathogenesis of sepsis associated encephalopathy (SAE). Given the mounting evidence of anti-inflammatory and neuroprotective effects of the cholinergic nervous system, it is surprising that there is little information about its changes in the brain during sepsis. To elucidate the role of the cholinergic nervous system in SAE, hippocampal choline acetyltransferase, muscarinic acetylcholine receptor-1, acetylcholinesterase and acetylcholine were evaluated in LPS-induced sepsis rats. Expression of pro-inflammatory cytokines, neuronal apoptosis, and animal cognitive performance were also assessed. Furthermore, therapeutic effects of the acetylcholinesterase inhibitor Huperzine A (HupA) on the hippocampal cholinergic nervous function and neuroinflammation were evaluated. A deficiency of the cholinergic nervous function was revealed in SAE, accompanied with over-expressed pro-inflammatory cytokines, increase in neuronal apoptosis and brain cognitive impairment. HupA remarkably promoted the deficient cholinergic nervous function and attenuated the abnormal neuroinflammation in SAE, paralleled with the recovery of brain function. We suggest that the deficiency of the cholinergic nervous function and the abnormal neuroinflammation are synergistically implicated in the pathogenesis of SAE. Thus, HupA is a potential therapeutic candidate for SAE, as it improves the deficient cholinergic nervous function and exerts anti-inflammatory action.
authors.affiliation: Southern Medical University, Guangzhou, Guangdong, China; Department of Emergency and Critical Care Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China; Department of Emergency, Guangzhou Medical University Affiliated Third Hospital, Guangzhou, Guangdong, China.
authors.forename: Sen-Zhi
authors.initials: SZ
authors.lastname: Zhu
authors.affiliation: Department of Emergency and Critical Care Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Huang
authors.affiliation: Department of Emergency and Critical Care Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
authors.forename: Lin-Qiang
authors.initials: LQ
authors.lastname: Huang
authors.affiliation: Department of Emergency and Critical Care Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
authors.forename: Yong-Li
authors.initials: YL
authors.lastname: Han
authors.affiliation: Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Qian-Peng
authors.initials: QP
authors.lastname: Han
authors.affiliation: Department of Emergency and Critical Care Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
authors.forename: Gao-Feng
authors.initials: GF
authors.lastname: Zhu
authors.affiliation: Department of Emergency and Critical Care Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
authors.forename: Miao-Yun
authors.initials: MY
authors.lastname: Wen
authors.affiliation: Department of Emergency and Critical Care Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China. Electronic address: yiyudeng666@163.com.
authors.forename: Yi-Yu
authors.initials: YY
authors.lastname: Deng
authors.affiliation: Southern Medical University, Guangzhou, Guangdong, China; Department of Emergency and Critical Care Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China. Electronic address: zenghongke@vip.163.com.
authors.forename: Hong-Ke
authors.initials: HK
authors.lastname: Zeng
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism*; D000470:Alkaloids / Q000008:administration & dosage*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage; D004660:Encephalitis / Q000209:etiology / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism*; D065166:Sepsis-Associated Encephalopathy / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D012717:Sesquiterpenes / Q000008:administration & dosage*; D065853:Spatial Learning / Q000187:drug effects; D065852:Spatial Memory / Q000187:drug effects
chemical_list: D000470:Alkaloids; D000893:Anti-Inflammatory Agents; D002800:Cholinesterase Inhibitors; D008070:Lipopolysaccharides; D011976:Receptors, Muscarinic; D012717:Sesquiterpenes; C050426:huperzine A; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D000109:Acetylcholine
keywords: Acetylcholine; Acetylcholinesterase; Choline acetyltransferase; Huperzine A; Muscarinic acetylcholine receptor 1; Sepsis associated encephalopathy