Affiliations: [a] Department of Pathology and Pathophysiology, Key Laboratory of Neurological Disease of National Education Ministry and Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China | [b] College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
Correspondence:
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Corresponding author: Dr. Q. Tian, Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Tel.: +86 27 83693883; Fax: +86 27 83693883; E-mail: tts0001@yahoo.cn and wangjz@mails.tjmu.edu.cn.
Note: [1] These authors contributed equally to the paper.
Abstract: 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.
Keywords: Alzheimer's disease, endoplasmic reticulum stress, light illumination, melatonin, tau
