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绿茶通过抑制 APP 裂解和预防 5XFAD 小鼠神经毒性来降低淀粉样 β 水平并改善认知障碍。

Green Tea Suppresses Amyloid β Levels and Alleviates Cognitive Impairment by Inhibiting APP Cleavage and Preventing Neurotoxicity in 5XFAD Mice.

机构信息

State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science & Technology, Anhui Agricultural University, Hefei, Anhui, 230036, P. R China.

Cancer Prevention Laboratory, Colorado State University, Fort Collins, CO, 80523, USA.

出版信息

Mol Nutr Food Res. 2021 Oct;65(19):e2100626. doi: 10.1002/mnfr.202100626. Epub 2021 Aug 16.

DOI:10.1002/mnfr.202100626
PMID:34342385
Abstract

SCOPE

The consumption of green tea is considered to be associated with a lower incidence of neurodegenerative diseases. In the present study, it is investigated the role of amyloid precursor protein cleavage, glial cell activation, neuroinflammation, and synaptic alterations in the protective effects of green tea against the amyloid β (Aβ) accumulation and cognitive impairment.

METHODS AND RESULTS

5XFAD mice are treated with green tea extract (GTE) for 8 or 16 weeks. Barnes maze and Y maze testing demonstrated that spatial learning and memory ability are markedly improved by GTE treatment. Immunofluorescence staining, ELISA, and western blot showed GTE significantly alleviate the formation of Aβ and reduce the levels of sAPPβ and C99, as well as sAPPα and C83. Meanwhile, GTE suppressed GFAP and Iba1 levels in the glial cells, increased PSD95 and synaptophysin levels in synaptic cells. Further, the IL-1β level is decreased, RNA sequencing reveals the genes annotated in response to stimulus and immune response are regulated.

CONCLUSION

Our findings indicate GTE suppresses Aβ levels and alleviate cognitive impairment in 5XFAD mice. These beneficial effects are accompanied by inhibition of APP cleavage pathways, suppression of glial cell activation and pro-inflammatory responses, and a reduction of synapse loss.

摘要

范围

饮用绿茶被认为与神经退行性疾病的发病率降低有关。本研究探讨了绿茶对淀粉样前体蛋白切割、神经胶质细胞激活、神经炎症和突触改变的保护作用,以防止淀粉样β(Aβ)积累和认知障碍。

方法和结果

用绿茶提取物(GTE)处理 5XFAD 小鼠 8 或 16 周。巴恩斯迷宫和 Y 迷宫测试表明,GTE 处理显著改善了空间学习和记忆能力。免疫荧光染色、ELISA 和 Western blot 显示,GTE 显著减轻了 Aβ的形成,降低了 sAPPβ和 C99以及 sAPPα和 C83的水平。同时,GTE 抑制了神经胶质细胞中的 GFAP 和 Iba1 水平,增加了突触细胞中 PSD95 和突触小体蛋白的水平。此外,IL-1β水平降低,RNA 测序显示,与刺激和免疫反应相关的基因被调控。

结论

我们的研究结果表明,GTE 可降低 5XFAD 小鼠的 Aβ水平并改善认知障碍。这些有益作用伴随着 APP 切割途径的抑制、神经胶质细胞激活和促炎反应的抑制以及突触丧失的减少。

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