Green tea catechins prevent cognitive deficits caused by Aβ1-40 in rats

Amyloid β peptide (Aβ)-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 Aβ1-40 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 Aβ) and the Aβ1-40-infused rat group (Aβ group), whereas the 0.5% PE group was divided into the PE+Vehicle group (PE-preadministered vehicle-infused rats) and the PE+Aβ group (PE-preadministered Aβ-infused rats). Aβ1-40 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 Aβ-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 Aβ-induced cognitive impairment by increasing antioxidative defenses.