title: Effects of alpha-lipoic acid on spatial learning and memory, oxidative stress, and central cholinergic system in a rat model of vascular dementia.
abstract: Brain oxidative stress due to chronic cerebral hypoperfusion was considered to be the major risk factor in the pathogenesis of vascular dementia. In this study, we investigated the protective efficacy of alpha-lipoic acid, an antioxidant, against vascular dementia in rats, as well as the potential mechanism. Bilateral common carotid arteries occlusion (BCCAO) induced severe cognitive deficits tested by Morris water maze (MWM), along with oxidative stress and disturbance of central cholinergic system. However, administration of alpha-lipoic acid (50mg/kg, i.p.) for 28 days significantly restored cognitive deficits induced by BCCAO. Biochemical determination revealed that alpha-lipoic acid markedly decreased the production of malondialdehyde (MDA) and the generation of reactive oxidative species (ROS), and increased the level of reduced glutathione (GSH) in the hippocampal tissue. Additionally, alpha-lipoic acid raised the level of acetylcholine (ACh) and choline acetyltransferase (ChAT) and decreased the activity of acetycholinesterase (AChE) in the hippocampus. These results indicated that treatment with alpha-lipoic acid significantly improved behavioral alterations, protected against oxidative stress, and restored central cholinergic system in the rat model of vascular dementia induced by BCCAO.
authors.affiliation: Department of Emergency, The First Hospital of Handan, Handan, Hebei 056002, PR China; Key Laboratory of Neurology of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050071, PR China. Electronic address: a34251900@163.com.
authors.forename: Ran-Ran
authors.initials: RR
authors.lastname: Zhao
authors.affiliation: Department of Neurology, The First Hospital of Handan, Handan, Hebei 056002, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Neurology, The First Hospital of Handan, Handan, Hebei 056002, PR China.
authors.forename: Xiao-Chen
authors.initials: XC
authors.lastname: Xu
authors.affiliation: Key Laboratory of Neurology of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050071, PR China.
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Tan
authors.affiliation: Department of Neurology, The Traditional Chinese Medicine Hospital of Anyang, Anyang, Henan 455000, PR China.
authors.forename: Liang-Min
authors.initials: LM
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The People's Hospital of Guangxi Zhuang Automous Region, Nanning, Guangxi 530021, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Emergency, The First Hospital of Handan, Handan, Hebei 056002, PR China.
authors.forename: Wen-Zhong
authors.initials: WZ
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The First Hospital of Handan, Handan, Hebei 056002, PR China.
authors.forename: Ji-Xiang
authors.initials: JX
authors.lastname: Liu
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D016893:Carotid Stenosis / Q000150:complications; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D015140:Dementia, Vascular / Q000209:etiology / Q000378:metabolism* / Q000523:psychology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D017208:Rats, Wistar; D065853:Spatial Learning / Q000187:drug effects*; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D008063:Thioctic Acid; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D000109:Acetylcholine
keywords: Acetylcholine; Bilateral common carotid artery occlusion; Chronic cerebral hypoperfusion; Morris water maze; Oxidative stress