title: The involvement of homocysteine in stress-induced Aβ precursor protein misprocessing and related cognitive decline in rats.
abstract: Chronic stress is a risk factor in the development of cognitive decline and even Alzheimer's disease (AD), although its underlying mechanism is not fully understood. Our previous data demonstrated that the level of homocysteine (Hcy) was significantly elevated in the plasma of stressed animals, which suggests the possibility that Hcy is a link between stress and cognitive decline. To test this hypothesis, we compared the cognitive function, plasma concentrations of Hcy, and the brain beta-amyloid (Aβ) level between rats with or without chronic unexpected mild stress (CUMS). A lower performance by rats in behavioral tests indicated that a significant cognitive decline was induced by CUMS. Stress also disturbed the normal processing of Aβ precursor protein (APP) and resulted in the accumulation of Aβ in the brains of rats, which showed a positive correlation with the hyperhomocysteinemia (HHcy) that appeared in stressed rats. Hcy-targeting intervention experiments were used to verify further the involvement of Hcy in stress-induced APP misprocessing and related cognitive decline. The results showed that diet-induced HHcy could mimic the cognitive impairment and APP misprocessing in the same manner as CUMS, while Hcy reduction by means of vitamin B complex supplements and betaine could alleviate the cognitive deficits and dysregulation of Aβ metabolism in CUMS rats. Taken together, the novel evidence from our present study suggests that Hcy is likely to be involved in chronic stress-evoked APP misprocessing and related cognitive deficits. Our results also suggested the possibility of Hcy as a target for therapy and the potential value of vitamin B and betaine intake in the prevention of stress-induced cognitive decline.
authors.affiliation: Department of Stress Medicine, Institute of Basic Medical Sciences, #27 Taiping Road, Haidian, Beijing, 100039, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.affiliation: Department of Stress Medicine, Institute of Basic Medical Sciences, #27 Taiping Road, Haidian, Beijing, 100039, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Stress Medicine, Institute of Basic Medical Sciences, #27 Taiping Road, Haidian, Beijing, 100039, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Stress Medicine, Institute of Basic Medical Sciences, #27 Taiping Road, Haidian, Beijing, 100039, People's Republic of China.
authors.forename: Jing-Bo
authors.initials: JB
authors.lastname: Gong
authors.affiliation: Department of Stress Medicine, Institute of Basic Medical Sciences, #27 Taiping Road, Haidian, Beijing, 100039, People's Republic of China.
authors.forename: Shi-Da
authors.initials: SD
authors.lastname: Wang
authors.affiliation: Department of Stress Medicine, Institute of Basic Medical Sciences, #27 Taiping Road, Haidian, Beijing, 100039, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Health and Environmental Medicine, Tianjin, 300050, People's Republic of China.
authors.forename: Xiu-Jie
authors.initials: XJ
authors.lastname: Gao
authors.affiliation: Department of Stress Medicine, Institute of Basic Medical Sciences, #27 Taiping Road, Haidian, Beijing, 100039, People's Republic of China. newjia@vip.sina.com.
authors.forename: Ling-Jia
authors.initials: LJ
authors.lastname: Qian
mesh_terms: D000544:Alzheimer Disease / Q000097:blood* / Q000523:psychology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D060825:Cognitive Dysfunction / Q000097:blood* / Q000523:psychology; D006624:Hippocampus / Q000378:metabolism; D006710:Homocysteine / Q000097:blood*; D008297:Male; D011499:Protein Processing, Post-Translational; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000097:blood* / Q000150:complications
chemical_list: D016564:Amyloid beta-Protein Precursor; D006710:Homocysteine
keywords: Beta-amyloid; Chronic unexpected mild stress; Cognitive decline; Homocysteine