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
小麦发布了新的文献求助10
2秒前
2秒前
丘比特应助雨季采纳,获得10
2秒前
nenoaowu发布了新的文献求助10
3秒前
深海鱼发布了新的文献求助50
5秒前
今天没烦恼完成签到 ,获得积分10
6秒前
JamesPei应助科研通管家采纳,获得10
11秒前
领导范儿应助科研通管家采纳,获得10
11秒前
Jasper应助科研通管家采纳,获得10
11秒前
bkagyin应助科研通管家采纳,获得10
11秒前
科目三应助科研通管家采纳,获得10
11秒前
桐桐应助科研通管家采纳,获得10
11秒前
11秒前
14秒前
15秒前
16秒前
万能图书馆应助米里迷路采纳,获得10
16秒前
高高的巨人完成签到 ,获得积分10
20秒前
--发布了新的文献求助10
21秒前
21秒前
凡人丿完成签到 ,获得积分10
22秒前
龙豆豆发布了新的文献求助10
23秒前
24秒前
26秒前
28秒前
chendz发布了新的文献求助10
30秒前
田野发布了新的文献求助30
31秒前
31秒前
31秒前
31秒前
31秒前
科研通AI2S应助东霓采纳,获得10
32秒前
33秒前
的速度发布了新的文献求助10
33秒前
啦啦啦发布了新的文献求助10
33秒前
33秒前
Ming发布了新的文献求助10
36秒前
36秒前
端庄的硕发布了新的文献求助10
36秒前
1renebaebae完成签到,获得积分10
37秒前
高分求助中
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
A new species of Coccus (Homoptera: Coccoidea) from Malawi 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 3183296
求助须知:如何正确求助?哪些是违规求助? 2833432
关于积分的说明 7994193
捐赠科研通 2495544
什么是DOI,文献DOI怎么找? 1331574
科研通“疑难数据库(出版商)”最低求助积分说明 636352
邀请新用户注册赠送积分活动 603509