期刊
AGE
卷 36, 期 4, 页码 -出版社
SPRINGER
DOI: 10.1007/s11357-014-9676-6
关键词
Alzheimer's disease; Polyprenols; D-galactose; Oxidative stress; Amyloid-beta (A beta)
资金
- National 12th Five-Year Plan Major Scientific and Technological Special Project for Significant New Drugs Creation project of Novel G protein-coupled receptor targeted drug screening system and key technology research [2012ZX09504001-001]
- Program for New Century Excellent Talents in University [NCET-10-0817]
- Major Scientific and Technological Special Project of Guangdong Province [2012A080201005]
- Fundamental Research Funds for the Central Universities [JKZ2009005, JKY2011052]
Cognitive deficiency and oxidative stress have been well documented in aging and in neurodegenerative disorders such as Alzheimer's disease. In this study, we assessed the therapeutic effect of polyprenols on D-galactose-induced cognitive impairment in mice by testing on of behavioral and cognitive performance. In order to explore the possible role of polyprenols against D-galactose-induced oxidative damages, we assessed various biochemical indicators. Chronic administration of D-galactose (150 mg/kg.d, s.c.) for 7 weeks significantly impaired cognitive performance (both in step-through passive and active avoidance tests) and locomotor activity (in open-field test) and the ability of spatial learning and memory (in Morris water maze test) compared with the control group. The results revealed that polyprenols treatment for 2 weeks significantly ameliorated model mice's cognitive performance and oxidative defense. All groups of polyprenols enhanced the learning and memory ability in step-through passive and active avoidance tests, locomotor activity in open-field test, and the ability of spatial learning and memory in Morris water maze test. Furthermore, high and middle level of polyprenols significantly increased total antioxidative capacity (T-AOC), glutathione peroxidase (GSH-Px), super oxide dismutase (SOD) activity, neprilysin (NEP), and beta-site A beta PP cleaving enzyme 1 (BACE1) expression, while nitric oxide (NO), nitric oxide synthase (NOS) activity, malondialdehyde (MDA) concentration, and the level of A beta 1-42 and presenilin 1 (PS1) were decreased. Polyprenols have a significant relieving effect on learning, memory, and spontaneous activities in a D-galactose-induced mouse model and ameliorates cognitive impairment and biochemical dysfunction in mice. In summary, we have demonstrated that polyprenols may ameliorate memory and cognitive impairment via enhancing oxidative defense and affecting generation and dissimilation of A beta-related enzymes, suggesting that polyprenols represent a novel drug for treating Alzheimer's disease.
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