The involvement of homocysteine in stress-induced Aβ precursor protein misprocessing and related cognitive decline in rats

Cell Stress and Chaperones - Tập 21 - Trang 915-926 - 2016
Fang Xie1, Yun Zhao1, Jing Ma1, Jing-Bo Gong1, Shi-Da Wang1, Liang Zhang1, Xiu-Jie Gao2, Ling-Jia Qian1
1Department of Stress Medicine, Institute of Basic Medical Sciences, Beijing, People’s Republic of China
2Institute of Health and Environmental Medicine, Tianjin, People’s Republic of China

Tóm tắt

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.

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Cell Stress and Chaperones

Tập 21

915-926

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