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鹅肌肽(β-丙氨酰-3-甲基-L-组氨酸)可改善老年 AβPPswe/PSEN1dE9 阿尔茨海默病模型小鼠的神经血管单元功能障碍和空间记忆。

Anserine (beta-alanyl-3-methyl-L-histidine) improves neurovascular-unit dysfunction and spatial memory in aged AβPPswe/PSEN1dE9 Alzheimer's-model mice.

机构信息

Department of Integrated Biosciences, The University of Tokyo, Kashiwa, Japan.

出版信息

Sci Rep. 2017 Oct 3;7(1):12571. doi: 10.1038/s41598-017-12785-7.

Abstract

Anserine/carnosine supplementation improves cerebral blood flow and verbal episodic memory in elderly people, as we previously reported. Anserine's buffering activity is superior to that of carnosine at neutral pH. In human sera, carnosine but not anserine is rapidly cleaved by carnosinase, limiting its effectiveness. This study examined the effects of anserine on AβPPswe/PSEN1dE9 Alzheimer's disease (AD) model mice over 18-months old, an age at which these mice exhibit detectable memory deficits. We found that 8 weeks of anserine treatment completely recovered the memory deficits, improved pericyte coverage on endothelial cells in the brain, and diminished chronic glial neuroinflammatory reactions in these mice. These results suggest that anserine (beta-alanyl-3-methyl-L-histidine) supplementation improved memory functions in AD-model mice by exerting a protective effect on the neurovascular units, which are composed of endothelial cells, pericytes, and supporting glial cells.

摘要

我们之前曾报道过,肌肽/鹅肌肽补充剂可改善老年人的大脑血流和情景记忆。在中性 pH 值下,肌肽的缓冲能力优于鹅肌肽。在人类血清中,肌肽而非鹅肌肽可被肌肽酶迅速切割,从而限制了其效果。本研究探讨了肌肽对 AβPPswe/PSEN1dE9 阿尔茨海默病(AD)模型小鼠的影响,这些小鼠在 18 个月大时出现可检测到的记忆缺陷。我们发现,8 周的肌肽治疗可完全恢复记忆缺陷,改善大脑内皮细胞上周细胞的覆盖,并减轻这些小鼠慢性胶质神经炎症反应。这些结果表明,肌肽(β-丙氨酰-3-甲基-L-组氨酸)通过对由内皮细胞、周细胞和支持性神经胶质细胞组成的神经血管单元发挥保护作用,改善了 AD 模型小鼠的记忆功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/101a/5626714/483a6a658dbd/41598_2017_12785_Fig1_HTML.jpg

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