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
虚幻的紫伊完成签到,获得积分10
1秒前
1秒前
MrZ关闭了MrZ文献求助
1秒前
van_发布了新的文献求助10
2秒前
屿杓发布了新的文献求助10
2秒前
5秒前
zhiyuan发布了新的文献求助30
5秒前
小兰花完成签到,获得积分10
5秒前
可爱的函函应助微笑采纳,获得10
6秒前
华仔应助执着的日记本采纳,获得10
6秒前
7秒前
888发布了新的文献求助10
8秒前
sunnn完成签到 ,获得积分10
8秒前
9秒前
活力的赛君完成签到,获得积分10
9秒前
11秒前
one发布了新的文献求助10
11秒前
liusen完成签到,获得积分10
11秒前
搜集达人应助酷酷的帽子采纳,获得10
11秒前
T012发布了新的文献求助10
13秒前
TOM发布了新的文献求助10
13秒前
13秒前
SciGPT应助危机的友绿采纳,获得10
15秒前
17秒前
微笑完成签到,获得积分10
17秒前
yc666发布了新的文献求助10
17秒前
我是老大应助糖果果采纳,获得10
17秒前
余泽完成签到 ,获得积分10
17秒前
随机子应助虚拟的秋寒采纳,获得10
17秒前
LCC发布了新的文献求助20
18秒前
rabwang发布了新的文献求助10
18秒前
橙子呀~完成签到 ,获得积分10
18秒前
Orange应助dxl采纳,获得10
19秒前
汉堡包应助赫赫采纳,获得10
19秒前
大模型应助ABS采纳,获得10
19秒前
T012完成签到,获得积分10
21秒前
Aggie发布了新的文献求助10
21秒前
21秒前
21秒前
21秒前
高分求助中
Spray / Wall-interaction Modelling by Dimensionless Data Analysis 2000
ALA生合成不全マウスでの糖代謝異常の分子機構解析 520
安全防范技术与工程 500
Mathematics and Finite Element Discretizations of Incompressible Navier—Stokes Flows 500
2-Acetyl-1-pyrroline: an important aroma component of cooked rice 500
A real-time energy management strategy based on fuzzy control and ECMS for PHEVs 400
2024 Medicinal Chemistry Reviews 400
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 3191167
求助须知:如何正确求助?哪些是违规求助? 2840526
关于积分的说明 8029016
捐赠科研通 2503954
什么是DOI,文献DOI怎么找? 1337245
科研通“疑难数据库(出版商)”最低求助积分说明 638034
邀请新用户注册赠送积分活动 606518