Elsevier

Neuroscience

Volume 159, Issue 4, 10 April 2009, Pages 1208-1215
Neuroscience

Behavioural Neuroscience
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

https://doi.org/10.1016/j.neuroscience.2009.02.008Get rights and content

Abstract

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 Ca2+/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.

Section snippets

Animals and supplementation

Female C57BL/6 J mice were provided by the Department of Laboratory Animal Science of Peking University Health Science Center and were housed five per cage with a 12-h dark/light cycle under controlled temperature (23±2 °C) and humidity (50%±10%). The animals had free access to food and water. After a 7-day acclimatization to the laboratory conditions, 14-month-old mice (n=60) were randomly divided into four groups: aged control group (n=15), 0.025% GTC-supplemented group (n=15), 0.05%

GTC intake and body weights

No deaths or obvious clinical signs were found in all groups throughout the experimental period. Daily water intake per mouse did not differ among the Aged control (4.27±0.06 ml/day), young control (4.33±0.05 ml/day), 0.025% GTC-treated (4.39±0.05 ml/day), 0.05% GTC-treated (4.37±0.04 ml/day) and 0.1% GTC-treated (4.29±0.06 ml/day) groups. The mean dose of GTC was therefore calculated to be about 40, 80 and 160 mg/kg/day. Body weights of mice submitted to GTC treatment were similar to that of

Discussion

The beneficial effects ascribed to tea drinking are believed to rely on the pharmacological actions of catechins and their derivatives. GTC are well absorbed in the intestine and metabolized in the liver. Several studies with chemiluminescence-based detection or HPLC have demonstrated that GTC or their derivatives can be detected in the brain following oral treatment, suggesting that they are able to cross the blood–brain barrier and thus have the potential to be active in vivo (Abd El Mohsen

Conclusion

In conclusion, the primary finding of this study is that GTC may be effective agents to prevent age-related learning and memory decline by modulating hippocampal CREB signaling cascade. Thus, drinking tea every day may improve the memory capabilities of elderly people and enhance their quality of life.

Acknowledgments

This work was supported by the foundation (No. 2006BAD27B08) from the Ministry of Science and Technology of the People's Republic of China.

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