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

Green Tea Suppresses Amyloid β Levels and Alleviates Cognitive Impairment by Inhibiting APP Cleavage and Preventing Neurotoxicity in 5XFAD Mice
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DOI:
10.1002/mnfr.202100626
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发表时间:
2021-08-16
影响因子:
5.2
通讯作者:
Wan, Xiaochun
Wan, Xiaochun
中科院分区:
农林科学2区
文献类型:
--
作者:
Kan, Zhipeng;Wang, Yijun;Wan, Xiaochun

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范围:绿色茶的消费被认为与神经退行性疾病的发病率较低有关。在本研究中,它是研究淀粉样前体蛋白裂解,神经胶质细胞活化,神经炎症和突触改变的保护作用的绿色茶对淀粉样蛋白β(A β)的积累和cognitive impairment.Methods和结果:5XFAD小鼠治疗绿色茶提取物(GTE)8或16周。巴恩斯迷宫和Y迷宫实验表明GTE能显著改善小鼠的空间学习记忆能力。免疫荧光染色、ELISA和western blot显示GTE显著减轻A β的形成,降低sAPP β和C99以及sAPP α和C83的水平。同时,GTE抑制胶质细胞中GFAP和Iba 1的表达,增加突触细胞中PSD 95和突触素的表达。此外,IL-1 β水平降低,RNA测序显示注释的基因响应刺激和免疫反应受到调节。结论:我们的研究结果表明GTE抑制5XFAD小鼠的A β水平并减轻认知障碍。这些有益作用伴随着APP裂解途径的抑制、神经胶质细胞活化和促炎反应的抑制以及突触损失的减少。
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 beta (A beta) 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 A beta and reduce the levels of sAPP beta and C99, as well as sAPP alpha and C83. Meanwhile, GTE suppressed GFAP and Iba1 levels in the glial cells, increased PSD95 and synaptophysin levels in synaptic cells. Further, the IL-1 beta level is decreased, RNA sequencing reveals the genes annotated in response to stimulus and immune response are regulated.Conclusion: Our findings indicate GTE suppresses A beta 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.