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通过增强胰岛素信号和改变肠道微生物组组成来提高海马淀粉样蛋白-β沉积,从而防止记忆功能障碍。

Protected against Memory Dysfunction by Elevating Hippocampal Amyloid-β Deposition through Potentiating Insulin Signaling and Altering Gut Microbiome Composition.

机构信息

Food & Nutrition, Obesity/Diabetes Center, Hoseo University, Asan 31499, Korea.

Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea.

出版信息

Int J Mol Sci. 2020 Apr 21;21(8):2900. doi: 10.3390/ijms21082900.

DOI:10.3390/ijms21082900
PMID:32326255
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7216031/
Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease. Herbal medicine may provide efficacious treatments for its prevention and/or cure. This study investigated whether a 70% ethanol extract of Kuntze (TTK; New Zealand spinach) improved the memory deficit by reducing hippocampal amyloid-β deposition and modulating the gut microbiota in rats with amyloid-β(25-35) infused into the hippocampus (AD rats) in an AD animal model. The AD rats had cellulose (AD-CON) or TTK (300 mg/kg bw; AD-TTK) in their high-fat diets for seven weeks. Rats with amyloid-β(35-25) infused into the hippocampus fed an AD-Con diet did not have memory loss (Normal-Con). AD-TTK protected against amyloid-β deposition compared to AD-Con, but it was higher than Normal-Con. AD-TTK protected against short-term and special memory loss measured by passive avoidance, Y maze, and water maze, compared to AD-Con. Compared to the Normal-Con, AD-Con attenuated hippocampal pCREB → pAkt → pGSK-3β, which was prevented in the AD-TTK group. Brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) mRNA expression decreased in the AD-CON group, and their expression was prevented in the AD-TTK group. Hippocampal TNF-α and IL-1β mRNA expressions were higher in the AD-Con group than in the Normal-Con, and AD-TTK groups protected against the increase in their expression. The AD-CON group showed an increase in insulin resistance compared to the Normal-Con group and the AD-TTK group showed improvement. AD-Con separated the gut microbiome community compared to the Normal-Con group and AD-TTK overlapped with the normal-Con. The AD-Con group had more , , and than the AD-TKK and Normal-Con group but fewer and . In conclusion, the 70% ethanol extract of TTK enhanced the memory function and potentiated hippocampal insulin signaling, reduced insulin resistance, and improved gut microbiota in amyloid-β-infused rats.

摘要

阿尔茨海默病(AD)是一种进行性神经退行性疾病。草药可能为其预防和/或治疗提供有效的治疗方法。本研究旨在探讨新西兰菠菜(TTK)的 70%乙醇提取物是否通过减少海马淀粉样β(Aβ)沉积和调节肠道微生物群来改善记忆缺陷,从而改善海马内注入 Aβ(25-35)的 AD 动物模型(AD 大鼠)中的大鼠的记忆缺陷。AD 大鼠在高脂饮食中添加纤维素(AD-CON)或 TTK(300mg/kg bw;AD-TTK),共七周。海马内注入 Aβ(35-25)并喂食 AD-Con 饮食的大鼠没有记忆丧失(Normal-Con)。与 AD-Con 相比,AD-TTK 可预防 Aβ 沉积,但高于 Normal-Con。与 AD-Con 相比,AD-TTK 可预防被动回避、Y 迷宫和水迷宫测量的短期和特殊记忆丧失。与 Normal-Con 相比,AD-Con 减弱了海马 pCREB→pAkt→pGSK-3β,而 AD-TTK 组则阻止了这一作用。脑源性神经营养因子(BDNF)和睫状神经营养因子(CNTF)mRNA 表达在 AD-CON 组中降低,而在 AD-TTK 组中则阻止了其表达。海马 TNF-α和 IL-1βmRNA 表达在 AD-Con 组中高于 Normal-Con 组,而 AD-TTK 组则阻止了其表达的增加。与 Normal-Con 组相比,AD-Con 组表现出胰岛素抵抗增加,而 AD-TTK 组则有所改善。与 Normal-Con 组相比,AD-Con 组的肠道微生物组群落分离,而 AD-TTK 组与 Normal-Con 重叠。AD-Con 组比 AD-TTK 和 Normal-Con 组有更多的 、 、和 ,但比 AD-TTK 和 Normal-Con 组有更少的 、 。总之,TTK 的 70%乙醇提取物增强了记忆功能,增强了海马胰岛素信号,降低了胰岛素抵抗,并改善了注入 Aβ的大鼠的肠道微生物群。

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