Effects of methionine intake on cognitive function in mild cognitive impairment patients and APP/PS1 Alzheimer's Disease model mice: Role of the cystathionine-β-synthase/H2S pathway
Yujia Xi,
Yuyu Zhang,
Yiwen Zhou,
Qing Liu,
Xuhui Chen,
Xuebo Liu,
Tilman Grune,
Lin Shi,
Min Hou,
Zhigang Liu
Affiliations
Yujia Xi
Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, 712100, China
Yuyu Zhang
Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, 712100, China
Yiwen Zhou
School of Public Health, College of Medicine, Shanghai Jiaotong University, Shanghai, 200025, China
Qing Liu
Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, 712100, China
Xuhui Chen
Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, 518000, China
Xuebo Liu
Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, 712100, China
Tilman Grune
German Institute of Human Nutrition (DIfE) Potsdam-Rehbruecke, Department of Molecular Toxicology, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany
Lin Shi
College of Food Engineering and Nutritional Science, Shaanxi Normal University, Shaanxi, 710119, China; Corresponding author.
Min Hou
School of Public Health, College of Medicine, Shanghai Jiaotong University, Shanghai, 200025, China; Corresponding author.
Zhigang Liu
Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, 712100, China; German Institute of Human Nutrition (DIfE) Potsdam-Rehbruecke, Department of Molecular Toxicology, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany; Northwest A&F University, Shenzhen Research Institute, Shenzen, Guangdong, 518000, China; Corresponding author. Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, 712100, China.
As a dietary intervention, methionine restriction (MR) has been reported to increase longevity and improve metabolism disorders. However, the effects of MR on alleviating neurodegenerative diseases such as Alzheimer's disease (AD) are largely unexplored. Here we sought to investigate the neuroprotective effects of low methionine intake in mild cognitive impairment (MCI) patients and APP/PS1 AD model mice, and to uncover the underlying mechanisms. In a cohort composed of 45 individuals diagnosed with MCI and 61 healthy controls without cognitive impairment, methionine intake was found to be positively associated with the increased risk of MCI, where no sex differences were observed. We further conducted a 16-week MR intervention (0.17% methionine, w/w) on APP/PS1 AD model mice. Although MR reduced Aβ accumulation in the brain of both male and female APP/PS1 mice, MR improved cognitive function only in male mice, as assessed by the Morris water maze test. Consistently, MR restored synapse ultrastructure and alleviated mitochondrial dysfunction by enhancing mitochondrial biogenesis in the brain of male APP/PS1 mice. Importantly, MR effectively balanced the redox status and activated cystathionine-β-synthase (CBS)/H2S pathway in the brain of male APP/PS1 mice. Together, our study indicated that lower dietary methionine intake is associated with improved cognitive function, in which CBS/H2S pathway plays an essential role. MR could be a promising nutritional intervention for preventing AD development.
