Drinking water temperature affects cognitive function and progression of Alzheimer’s disease in a mouse model

Jiang-ping Wei1,2, Wen Wen1,2, Yuan Dai2,3, Li-xia Qin1,2, Yue-qiang Wen2,4, Dayue Darrel Duan5, Shi-jun Xu1,2
1 School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
2 Institute of Material Medica Integration and Transformation for Brain Disorders, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
3 School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
4 School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
5 Center for Phenomics of Traditional Chinese Medicine and the Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou 646000, China
Correspondence to: Dayue Darrel Duan:, Shi-jun Xu:,
DOI: 10.1038/s41401-020-0407-5
Received: 1 September 2019
Accepted: 23 March 2020
Advance online: 25 May 2020


Lifestyle factors may affect mental health and play a critical role in the development of neurodegenerative diseases including Alzheimer’s disease (AD). However, whether the temperatures of daily beverages have any impact on cognitive function and AD development has never been studied. In this study, we investigated the effects of daily drinking water temperatures on cognitive function and AD development and progression in mice and the underlying mechanisms. Cognitive function of mice was assessed using passive avoidance test, open field test, and Morris water maze. Wild-type Kunming mice receiving intragastric water (IW, 10 mL/kg, 2 times/day) at 0 °C for consecutive 15 days displayed significant cognitive defects accompanied by significant decrease in gain of body weight, gastric emptying rate, pepsin activity, and an increase in the energy charge in the cortex when compared with mice receiving the same amount of IW at 25 °C (a temperature mimicking most common drinking habits in human), suggesting the altered neuroenergetics may cause cognitive decline. Similarly, in the transgenic APPwse/PS1De9 familial AD mice and their age- and gender-matched wild-type C57BL/6 mice, receiving IW at 0 °C, but not at 25 °C, for 35 days caused a significant time-dependent decrease in body weight and cognitive function, accompanied by a decreased expression of PI3K, Akt, the glutamate/GABA ratio, as well as neuropathy with significant amyloid lesion in the cortex and hippocampus. All of these changes were significantly aggravated in the APPwse/PS1De9 mice than in the control C57BL/6 mice. These data demonstrate that daily beverage at 0 °C may alter brain insulin-mediated neuroenergetics, glutamate/GABA ratio, cause cognitive decline and neuropathy, and promote AD progression.
Keywords: Alzheimer’s disease; cognition; drinking water; temperature; glutamate; GABA; insulin signaling; APPwse/PS1De9 familial AD mice

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