(-)-Gallocatechin gallate from green tea rescues cognitive impairment through restoring hippocampal silent synapses in post-menopausal depression

绿茶中的 (-)-没食子儿茶素没食子酸酯可通过恢复绝经后抑郁症患者的海马静默突触来挽救认知障碍

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作者:Sukjin Ko #, Won Seuk Jang #, Ji-Hyun Jeong, Ji Woong Ahn, Young-Hwan Kim, Sohyun Kim, Hyeon Kyeong Chae, Seungsoo Chung

Abstract

Post-menopausal depression (PMD) is a common psychological disorder accompanied by a cognitive deficit, which is caused by a series of uncontrolled emotional disruptions by strong environmental stressors during menopause. To overcome PMD-induced cognitive deficit, Green tea has been suggested as a dietary supplement because of its ameliorating effect on cognitive dysfunction induced by normal aging or neurodegenerative syndromes; however, its clinical use to improve PMD-accompanied cognitive deficit is still limited due to the controversy for the active ingredients and ambiguous mechanism of its action. Here, we developed modified high-temperature-processed green tea extract (HTP-GTE), which showed lower neuronal toxicity than the conventional green tea extract (GTE). We also demonstrated that HTP-GTE administration prevented the development of learned helplessness (LH) in a rat post-menopausal model. Additionally, HTP-GTE improved LH-induced cognitive impairments simultaneously with rescued the long-term synaptic plasticity. This occurred via the restoration of silent synapse formation by increasing the hippocampal BDNF-tyrosine receptor kinase B pathway in the helpless ovariectomized (OVX) rats. Likewise, we also identified that (-)-gallocatechin gallate was the main contributor of the HTP-GTE effect. Our findings suggested that HTP-GTE has a potential as a preventive nutritional supplement to ameliorate cognitive dysfunctions associated with PMD.

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