Protective effects of trans-2, 4-dimethoxystibene on cognitive, impairments induced by Aβ25-35 in, hypercholesterolemic rats

被引：23

作者：

Ruan, Can-Jun ^{[1
]}

Li, Zhan ^{[2
,3
]}

Zhang, Li ^{[4
,5
]}

Chen, Di-Hua ^{[2
,3
]}

Du, Guan-Hua ^{[4
,5
]}

Sun, Lan ^{[1
]}

机构：

[1] Chinese Acad Sci, Sch Basic Med, Peking Union Med Coll, Dept Pharmacol,Inst Basic Med Sci, Beijing 100005, Peoples R China

[2] Chinese Acad Med Sci, Inst Med Plant Dev, Beijing 100094, Peoples R China

[3] Peking Union Med Coll, Beijing 100094, Peoples R China

[4] Chinese Acad Med Sci, Inst Mat Med, Natl Ctr Pharmaceut Screening, Beijing 100050, Peoples R China

[5] Peking Union Med Coll, Beijing 100050, Peoples R China

来源：

BRAIN RESEARCH BULLETIN | 2010年 / 82卷 / 5-6期

关键词：

Alzheimer's disease; Hypercholesterolemia; Oxidative; Stilbene; Neuroprotective; A beta(25-35); ALZHEIMERS-DISEASE BRAIN; AMYLOID-BETA; OXIDATIVE STRESS; TOTAL CHOLESTEROL; APOLIPOPROTEIN-E; SENILE PLAQUES; IN-VITRO; PROTEIN; NEURODEGENERATION; NEUROTOXICITY;

D O I：

10.1016/j.brainresbull.2010.04.016

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Trans-2, 4-dimethoxystibene (S3) is a synthetic stilbenes. In the present study, 53 was investigated to assess its neuroprotective effect against the toxicity induced by A beta(25-35) in hypercholesterolemic rats. Rats were fed with hypercholesterolemic chow for six weeks, and then received a single intracerebroventricular (icy.) injection of A beta(25-35) and a treatment with S3 or estradiol (E2). Behavioral changes and neuron apoptosis in rats were evaluated using Morris water maze, step-down test and TUNEL tests. To further explore the mechanism of S3, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), choline acetyl transferase (ChAT), acetylcholine esterase (AchE) and the contents of malondialdehyde (MDA) in hippocampus were analyzed by spectrophotometric method. At the same time, the releases of cytochrome C were analyzed by Western Blot, and the contents of acetylcholine (Ach) were analyzed by Elisa. The data showed that consumption of S3 (50 mg/kg/d) significantly ameliorated the cognitive deficits and neuron apoptosis caused by i.c.v, injection of A beta(25-35). Meanwhile, S3 reversed the decreased activity of ChAT, SOD, GSH-Px and contents of Ach, as well as the increased activity of AchE, MDA contents and the release of cytochrome C in hippocampus. These findings suggest that S3 may be a potential candidate for development as therapeutic agent to treat AD through regulating cholinergic nerve system and anti-oxidative mechanism. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：251 / 258

页数：8

共 38 条

[21] The levels of soluble amyloid beta in different high density lipoprotein subfractions distinguish Alzheimer's and normal aging cerebrospinal fluid: implication for brain cholesterol pathology? [J].