Dietary Xylitol Supplement Ameliorated AD-related Neuronal Injury by Regulating Glucose Metabolism Relevant Amino Acids in Mice.

IF 2.7 4区 医学 Q3 NEUROSCIENCES CNS & neurological disorders drug targets Pub Date : 2023-01-01 DOI:10.2174/1871527322666220922112955
Mengjia Jin, Xintong Ji, Xiaozheng Zhu, Yikai Shou, Zhiwei Ge, Huanhuan Wang
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Abstract

Background: Alzheimer's disease (AD) is one of the most common irreversible degenerative diseases of the central nervous system. Recent studies have found that patients with AD generally experience abnormal glucose metabolism. Xylitol is a functional sugar alcohol, which has been reported to regulate glucose metabolism.

Objective: The present study was designed to determine whether xylitol can alleviate cognitive impairment in AD mice.

Methods: In the current research, 5% xylitol was supplemented in the diet to treat APP/PS1 transgenic AD mice for 2 months. Cognitive ability was measured by the Morris water maze, and anxiety-like behaviors were examined by open-field experiment. Hippocampal cellular apoptosis and mitochondria pathway related apoptotic proteins were tested by TUNEL staining and immunoblotting, respectively. By LC-MS, plasma levels of glucose metabolism intermediates and related amino acids were evaluated.

Results: Results showed that xylitol could significantly ameliorate anxiety-like activity in AD mice by partially regulating expression levels of mitochondrial pathway-related apoptotic proteins. Xylitolregulated glucose metabolism may play an important role in the process.

Conclusion: The current study suggests that xylitol may be a potential candidate for improving neuropsychiatric behavior in AD by regulating the levels of TCA cycle intermediates and related amino acids in glucose metabolism.

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膳食补充木糖醇通过调节小鼠葡萄糖代谢相关氨基酸改善ad相关神经元损伤。
背景:阿尔茨海默病(AD)是最常见的中枢神经系统不可逆退行性疾病之一。最近的研究发现,AD患者普遍存在糖代谢异常。木糖醇是一种功能性糖醇,据报道具有调节葡萄糖代谢的作用。目的:研究木糖醇是否能减轻AD小鼠的认知功能障碍。方法:本研究在日粮中添加5%木糖醇,治疗APP/PS1转基因AD小鼠2个月。采用Morris水迷宫测试认知能力,开放性实验测试类焦虑行为。TUNEL染色和免疫印迹法分别检测海马细胞凋亡和线粒体通路相关凋亡蛋白。采用LC-MS法测定糖代谢中间体及相关氨基酸的血浆水平。结果:木糖醇可通过部分调节线粒体通路相关凋亡蛋白的表达水平,显著改善AD小鼠的焦虑样活性。木糖醇调节的葡萄糖代谢可能在这一过程中起重要作用。结论:目前的研究表明木糖醇可能是通过调节葡萄糖代谢中TCA循环中间体和相关氨基酸水平来改善AD患者神经精神行为的潜在候选者。
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来源期刊
CiteScore
5.10
自引率
3.30%
发文量
158
审稿时长
6-12 weeks
期刊介绍: Aims & Scope CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. CNS & Neurological Disorders - Drug Targets publishes guest edited thematic issues written by leaders in the field covering a range of current topics of CNS & neurological drug targets. The journal also accepts for publication original research articles, letters, reviews and drug clinical trial studies. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal is essential reading for all pharmaceutical scientists involved in drug discovery and development.
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