PMID- 19409206 OWN - NLM STAT- MEDLINE DCOM- 20090820 LR - 20171116 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 159 IP - 4 DP - 2009 Apr 10 TI - Long-term administration of green tea catechins prevents age-related spatial learning and memory decline in C57BL/6 J mice by regulating hippocampal cyclic amp-response element binding protein signaling cascade. PG - 1208-15 LID - 10.1016/j.neuroscience.2009.02.008 [doi] AB - Flavonoid-rich foods have been shown to be effective at reversing age-related deficits in learning and memory in both animals and humans. However, little investigation of the preventative effects of flavonoids on the naturally aged animals was reported. In our study, 14-month-old female C57BL/6 J mice were orally administered 0.025%, 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 age-related spatial learning and memory decline of mice in the Morris water maze. Better performance of GTC-treated mice was associated with increased levels of cAMP-response element binding protein (CREB) phosphorylation in the hippocampus. The expressions of brain-derived neurotrophic factor (BDNF) and Bcl-2, two target genes of CREB which can exhibit long-term regulatory roles in synaptic plasticity and synaptic structure, were also increased. We also found that long-term 0.05% or 0.1% GTC administration prevented age-related reductions of two representative post-synaptic density proteins PSD95 and Ca(2+)/calmodulin-dependent protein kinase II, suggesting that synaptic structural changes may be involved. These results demonstrated that long-term 0.05% or 0.1% green tea catechin administration may prevent age-related spatial learning and memory decline of female C57BL/6 J mice by regulating hippocampal CREB signaling cascade. FAU - Li, Q AU - Li Q AD - Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, PR China. FAU - Zhao, H F AU - Zhao HF FAU - Zhang, Z F AU - Zhang ZF FAU - Liu, Z G AU - Liu ZG FAU - Pei, X R AU - Pei XR FAU - Wang, J B AU - Wang JB FAU - Cai, M Y AU - Cai MY FAU - Li, Y AU - Li Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090211 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Antioxidants) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Creb1 protein, mouse) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Disks Large Homolog 4 Protein) RN - 0 (Dlg4 protein, mouse) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Membrane Proteins) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 8R1V1STN48 (Catechin) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2) RN - EC 2.7.4.8 (Guanylate Kinases) SB - IM MH - Aging/drug effects MH - Animals MH - Antioxidants/*administration & dosage MH - Brain-Derived Neurotrophic Factor/metabolism MH - Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism MH - Catechin/*administration & dosage MH - Cyclic AMP Response Element-Binding Protein/*metabolism MH - Disks Large Homolog 4 Protein MH - Female MH - Guanylate Kinases MH - Hippocampus/drug effects MH - Intracellular Signaling Peptides and Proteins/metabolism MH - Learning/*drug effects MH - Maze Learning/drug effects MH - Membrane Proteins/metabolism MH - Memory/*drug effects MH - Mice MH - Mice, Inbred C57BL MH - Phosphorylation MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - Random Allocation MH - Signal Transduction/drug effects MH - Space Perception/*drug effects EDAT- 2009/05/05 09:00 MHDA- 2009/08/21 09:00 CRDT- 2009/05/05 09:00 PHST- 2008/11/22 00:00 [received] PHST- 2009/01/12 00:00 [revised] PHST- 2009/02/04 00:00 [accepted] PHST- 2009/05/05 09:00 [entrez] PHST- 2009/05/05 09:00 [pubmed] PHST- 2009/08/21 09:00 [medline] AID - S0306-4522(09)00187-0 [pii] AID - 10.1016/j.neuroscience.2009.02.008 [doi] PST - ppublish SO - Neuroscience. 2009 Apr 10;159(4):1208-15. doi: 10.1016/j.neuroscience.2009.02.008. Epub 2009 Feb 11.