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Drinking water temperature affects cognitive function and progression of Alzheimer’s disease in a mouse model
引用本文:Jiang-ping Wei,Wen Wen,Yuan Dai,Li-xia Qin,Yue-qiang Wen,Dayue Darrel Duan,Shi-jun Xu. Drinking water temperature affects cognitive function and progression of Alzheimer’s disease in a mouse model[J]. Acta pharmacologica Sinica, 2021, 42(1): 45-54. DOI: 10.1038/s41401-020-0407-5
作者姓名:Jiang-ping Wei  Wen Wen  Yuan Dai  Li-xia Qin  Yue-qiang Wen  Dayue Darrel Duan  Shi-jun Xu
作者单位:School of Pharmacy;Institute of Material Medica Integration and Transformation for Brain Disorders;School of Health Preservation and Rehabilitation;School of Basic Medicine;Center for Phenomics of Traditional Chinese Medicine and the Affiliated Traditional Chinese Medicine Hospital
基金项目:This work was supported by the National Natural Science Foundation of China(Key Program;No.81430100 to SX);by the Science and Technology Strategic Cooperation Programs of Luzhou Municipal People's Government and Southwest Medical University(Nos.2017LZXNYD-P01 and 2019LZXNYD-Duan Team to DDD)。
摘    要: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℃ 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℃(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℃,but not at 25℃,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℃ may alter brain insulin-mediated neuroenergetics,glutamate/GABA ratio,cause cognitive decline and neuropathy,and promote AD progression.

关 键 词:Alzheimer’s  disease  COGNITION  drinking  water  temperature  GLUTAMATE  GABA  insulin  signaling  APPwse/PS1De9  familial  AD  mice
收稿时间:2019-09-01

Drinking water temperature affects cognitive function and progression of Alzheimer’s disease in a mouse model
Jiang-ping Wei,Wen Wen,Yuan Dai,Li-xia Qin,Yue-qiang Wen,Dayue Darrel Duan,Shi-jun Xu. Drinking water temperature affects cognitive function and progression of Alzheimer’s disease in a mouse model[J]. Acta pharmacologica Sinica, 2021, 42(1): 45-54. DOI: 10.1038/s41401-020-0407-5
Authors:Jiang-ping Wei  Wen Wen  Yuan Dai  Li-xia Qin  Yue-qiang Wen  Dayue Darrel Duan  Shi-jun Xu
Abstract: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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