LONG-TERM GREEN TEA CATECHIN ADMINISTRATION PREVENTS SPATIAL LEARNING AND MEMORY IMPAIRMENT IN SENESCENCE-ACCELERATED MOUSE PRONE-8 MICE BY DECREASING Aβ1-42 OLIGOMERS AND UPREGULATING SYNAPTIC PLASTICITY-RELATED PROTEINS IN THE HIPPOCAMPUS

The senescence-accelerated mouse prone-8 (SAMP8) is characterized by early onset of learning and memory deficits along with spontaneous overproduction of soluble beta-amyloid peptide (A beta) in the brain. In our study, 4 month old male SAMP8 mice were orally administered 0.05% and 0.1% green tea catechins (GTC, w/v) in drinking water for 6 months. We found that a supplementation with 0.05% or 0.1% GTC prevented spatial learning and memory impairments of mice in the Morris water maze. Better performance of GTC-treated mice was associated with decreased levels of A beta(1-42) oligomers in the hippocampus. The activity of the protein kinase A/cAMP-response element binding protein (PKA/CREB) pathway, one of the molecular targets of A beta oligomers which is crucial for late long-term potentiation and long-term memory formation, was significantly increased after GTC administration. We also found that chronic 0.05% or 0.1% GTC consumption prevented the reductions of three representative proteins of synaptic function and synaptic structure, including brain-derived neurotrophic factor(BDNF), post-synaptic density protein-95 (PSD95) and Ca2+/calmodulin-dependent protein kinase 11 (CaMKII). These results demonstrated that long-term 0.05% or 0.1% green tea catechin administration may prevent spatial learning and memory decline of SAMP8 mice by decreasing A beta(1-42) oligomers and upregulating synaptic plasticity-related proteins in the hippocampus. (c) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.