Chronic rapid eye movement sleep deprivation aggravates the pathogenesis of Alzheimer’s disease by decreasing brain O-GlcNAc cycling in mice

发病机制 快速眼动睡眠 神经学 疾病 睡眠剥夺 神经科学 医学 阿尔茨海默病 睡眠(系统调用) 眼球运动 心理学 内科学 昼夜节律 计算机科学 操作系统
作者
Dong Yeol Kim,Sang-Min Kim,Inn‐Oc Han
出处
期刊:Journal of Neuroinflammation [Springer Nature]
卷期号:21 (1) 被引量:1
标识
DOI:10.1186/s12974-024-03179-4
摘要

This study investigated the role of O-GlcNAc cycling in Alzheimer's disease-related changes in brain pathophysiology induced by chronic REM sleep deprivation (CSD) in mice. CSD increased amyloid beta (Aβ) and p-Tau accumulation and impaired learning and memory (L/M) function. CSD decreased dendritic length and spine density. CSD also increased the intensity of postsynaptic density protein-95 (PSD-95) staining. All of these Alzheimer's disease (AD) pathogenic changes were effectively reversed through glucosamine (GlcN) treatment by enhancing O-GlcNAcylation. Interestingly, the lelvel of O-GlcNAcylated-Tau (O-Tau) exhibited an opposite trend compared to p-Tau, as it was elevated by CSD and suppressed by GlcN treatment. CSD increased neuroinflammation, as indicated by elevated levels of glial fibrillary acidic protein and IBA-1-positive glial cells in the brain, which were suppressed by GlcN treatment. CSD promoted the phosphorylation of GSK3β and led to an upregulation in the expression of endoplasmic reticulum (ER) stress regulatory proteins and genes. These alterations were effectively suppressed by GlcN treatment. Minocycline not only suppressed neuroinflammation induced by CSD, but it also rescued the decrease in O-GlcNAc levels caused by CSD. Minocycline also reduced AD neuropathy without affecting CSD-induced ER stress. Notably, overexpressing O-GlcNAc transferase in the dentate gyrus region of the mouse brain rescued CSD-induced cognitive dysfunction, neuropathy, neuroinflammation, and ER stress responses. Collectively, our findings reveal that dysregulation of O-GlcNAc cycling underlies CSD-induced AD pathology and demonstrate that restoration of OGlcNAcylation protects against CSD-induced neurodegeneration.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
丘比特应助西瓜珺采纳,获得10
刚刚
今夜无人入眠完成签到,获得积分10
1秒前
于芋菊举报研友_8QQ7D8求助涉嫌违规
1秒前
鲤鱼晓绿完成签到,获得积分10
2秒前
2秒前
不配.应助科研通管家采纳,获得10
4秒前
脑洞疼应助科研通管家采纳,获得10
4秒前
香蕉觅云应助科研通管家采纳,获得10
4秒前
4秒前
123mmmm完成签到,获得积分10
5秒前
鲤鱼晓绿发布了新的文献求助10
5秒前
一言一木发布了新的文献求助10
8秒前
赖向珊发布了新的文献求助10
10秒前
大个应助包容的琦采纳,获得10
13秒前
慕青应助研友_nPoXoL采纳,获得10
14秒前
14秒前
无醇橙汁关注了科研通微信公众号
16秒前
18秒前
19秒前
西瓜珺发布了新的文献求助10
19秒前
20秒前
wanci应助江小鱼在查文献采纳,获得10
20秒前
Erica完成签到,获得积分10
20秒前
23秒前
23秒前
23秒前
蒙扎发布了新的文献求助10
24秒前
陈露发布了新的文献求助10
26秒前
26秒前
所所应助爱做实验的泡利采纳,获得10
27秒前
27秒前
一目发布了新的文献求助10
28秒前
POPO完成签到 ,获得积分10
28秒前
31秒前
烟花应助阿菜采纳,获得10
32秒前
一言一木完成签到,获得积分10
32秒前
32秒前
冬去春来发布了新的文献求助10
32秒前
33秒前
小熊座a完成签到 ,获得积分10
33秒前
高分求助中
Spray / Wall-interaction Modelling by Dimensionless Data Analysis 2000
Evolution 3rd edition 1500
保险藏宝图 1000
Lire en communiste 1000
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 700
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 700
Mathematics and Finite Element Discretizations of Incompressible Navier—Stokes Flows 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3185922
求助须知:如何正确求助?哪些是违规求助? 2836260
关于积分的说明 8008368
捐赠科研通 2498681
什么是DOI,文献DOI怎么找? 1333725
科研通“疑难数据库(出版商)”最低求助积分说明 636910
邀请新用户注册赠送积分活动 604738