Green tea catechins prevent cognitive deficits caused by Abeta1-40 in rats.
Amyloid beta peptide (Abeta)-induced oxidative stress is involved in the pathogenesis of Alzheimer's disease (AD). In contrast, green tea catechins confer potent antioxidative defense to brain neurons. Therefore, we examined whether long-term administration of green tea catechins [Polyphenon E (PE): 63% of epigallocatechin-3-gallate, 11% of epicatechin, 6% of (-)-epigallocatechin and 6% of (-)-epicatechin-gallate] prevents cognitive impairment in an animal model of AD, rats infused with Abeta1-40 into the cerebral ventricle. Five-week-old male Wistar rats fed with an MF diet were randomly divided into two groups: 0.0% PE (rats administered with water only) and 0.5% PE (rats administered with 5 g/L of PE). Twenty weeks after the PE administration, the 0.0% PE group was divided into the Vehicle group (rats infused with the solvent used for dissolving Abeta) and the Abeta(1-40)-infused rat group (Abeta group), whereas the 0.5% PE group was divided into the PE+Vehicle group (PE-preadministered vehicle-infused rats) and the PE+Abeta group (PE-preadministered Abeta-infused rats). Abeta1-40 or vehicle was infused into the cerebral ventricle using a mini osmotic pump. Behavioral changes in the rats were assessed by an eight-arm radial maze. PE administration for 26 weeks significantly decreased the Abeta-induced increase in the number of reference and working memory errors, with a concomitant reduction of hippocampal lipid peroxide (LPO; 40%) and cortico-hippocampal reactive oxygen species (ROS; 42% and 50%, respectively). Significantly reduced levels of LPO in the plasma (24%) and hippocampus (25%) as well as those of ROS in the hippocampus (23%) and cortex (41%) were found in the PE+Vehicle group as compared with the Vehicle group. Furthermore, rats with preadministered PE had higher ferric-reducing antioxidation power of plasma as compared with the Vehicle group. Our results suggest that long-term administration of green tea catechins provides effective prophylactic benefits against Abeta-induced cognitive impairment by increasing antioxidative defenses.
Haque
Abdul M
AM
Department of Environmental Physiology, Faculty of Medicine, Shimane University, Izumo City, Shimane, 693-8501, Japan.
Hashimoto
Michio
M
Katakura
Masanori
M
Hara
Yukihiko
Y
Shido
Osamu
O
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood; D005290:Ferric Compounds / Q000097:blood; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013662:Tea; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D016229:Amyloid beta-Peptides; D005290:Ferric Compounds; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D013662:Tea; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides; C078592:amyloid beta-protein (1-40); D002392:Catechin; D002784:Cholesterol; C472086:polyphenon E