Constant Illumination Induces Alzheimer-Like Damages with Endoplasmic Reticulum Involvement and the Protection of Melatonin

被引：57

作者：

Ling, Zhi-Qun ^{[1
,2
]}

Tian, Qing ^{[1
]}

Wang, Li ^{[1
]}

Fu, Zheng-Qi ^{[1
]}

Wang, Xiao-Chuan ^{[1
]}

Wang, Qun ^{[1
]}

Wang, Jian-Zhi ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Key Lab Neurol Dis Natl Educ Minist & Hubei Prov, Dept Pathol & Pathophysiol, Wuhan 430030, Peoples R China

[2] Chengdu Univ Tradit Chinese Med, Coll Pharm, Chengdu, Peoples R China

来源：

JOURNAL OF ALZHEIMERS DISEASE | 2009年 / 16卷 / 02期

关键词：

Alzheimer's disease; endoplasmic reticulum stress; light illumination; melatonin; tau; GLYCOGEN-SYNTHASE KINASE-3; N-TERMINAL KINASE; PHOSPHORYLATES TAU-PROTEIN; SPATIAL MEMORY RETENTION; RAT-BRAIN; OXIDATIVE STRESS; TRANSGENIC MICE; OKADAIC ACID; MOUSE MODEL; A-BETA;

D O I：

10.3233/JAD-2009-0949

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Most patients with Alzheimer's disease (AD) present decreased levels of melatonin, a day-night rhythm-related hormone. To investigate the role of melatonin deficiency in AD, we used constant illumination to interrupt melatonin metabolism and measured some of the AD-like alterations in rats. Concomitant with decreased serum melatonin, the rats developed spatial memory deficits, tau hyperphosphorylation at multiple sites, activation of glycogen synthase kinase-3 and protein kinase A, as well as suppression of protein phosphatase-1. Prominent oxidative damage and organelle lesions, demonstrated by increased expression of endoplasmic reticulum (ER) stress-related proteins including BiP/GRP78 and CHOP/GADD153, decreased number of rough ER and free ribosome, thinner synapses, and increased superoxide dismutase and monoamine oxidase were also observed in the light exposed rats. Simultaneous supplement of melatonin partially arrested the behavioral and molecular impairments. It is suggested that melatonin deficiency may be an upstream effector responsible for the AD-like behavioral and molecular pathologies with ER stress-involved mechanisms.

引用

页码：287 / 300

页数：14

共 82 条

[21] Tau protein is cross-linked by transglutaminase in P301L tau transgenic mice [J].