| Aquaporin 4 deficiency eliminates the beneficial effects of voluntary exercise in a mouse model of Alzheimer’s disease |
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| 作者姓名： | Yun Liu Pan-Pan Hu Shuang Zhai Wei-Xi Feng Rui Zhang Qian Li Charles Marshall Ming Xiao Ting Wu |
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| 作者单位： | Department of Neurology;Jiangsu Province Key Laboratory of Neurodegeneration;Brain Institute;College of Health Sciences |
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| 基金项目： | supported by the National Natural Science Foundation of China,No.81772454(to TW);Natural Science Foundation of Jiangsu,China,No.BK20190655(to QL). |
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| 摘 要： | Regular exercise has been shown to reduce the risk of Alzheimer’s disease(AD).Our previous study showed that the protein aquaporin 4(AQP4),which is specifically expressed on the paravascular processes of astrocytes,is necessary for glymphatic clearance of extracellular amyloid beta(Aβ)from the brain,which can delay the progression of Alzheimer’s disease.However,it is not known whether AQP4-regulated glymphatic clearance of extracellular Aβis involved in beneficial effects of exercise in AD patients.Our results showed that after 2 months of voluntary wheel exercise,APP/PS1 mice that were 3 months old at the start of the intervention exhibited a decrease in Aβburden,glial activation,perivascular AQP4 mislocalization,impaired glymphatic transport,synapse protein loss,and learning and memory defects compared with mice not subjected to the exercise intervention.In contrast,APP/PS1 mice that were 7 months old at the start of the intervention exhibited impaired AQP4 polarity and reduced glymphatic clearance of extracellular Aβ,and the above-mentioned impairments were not alleviated after the 2-month exercise intervention.Compared with age-matched APP/PS1 mice,AQP4 knockout APP/PS1 mice had more serious defects in glymphatic function,Aβplaque deposition,and cognitive impairment,which could not be alleviated after the exercise intervention.These findings suggest that AQP4-dependent glymphatic transport is the neurobiological basis for the beneficial effects of voluntary exercises that protect against the onset of AD.
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| 关 键 词： | Alzheimer’s disease AMYLOID-BETA ASTROCYTES AQUAPORIN-4 glymphatic system learning and memory synaptic protein transgenic mice voluntary exercise |
| 收稿时间： | 2021 May 6 |
Aquaporin 4 deficiency eliminates the beneficial effects of voluntary exercise in a mouse model of Alzheimer's disease |
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| Yun Liu,Pan-Pan Hu,Shuang Zhai,Wei-Xi Feng,Rui Zhang,Qian Li,Charles Marshall,Ming Xiao,Ting Wu.Aquaporin 4 deficiency eliminates the beneficial effects of voluntary exercise in a mouse model of Alzheimer's disease[J].Neural Regeneration Research,2022,17(9):2079-2088. |
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| Authors: | Yun Liu Pan-Pan Hu Shuang Zhai Wei-Xi Feng Rui Zhang Qian Li Charles Marshall Ming Xiao Ting Wu |
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| Institution: | 1.Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China;2.Jiangsu Province Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, Jiangsu Province, China;3.Brain Institute, the Affiliated Nanjing Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China;4.College of Health Sciences, University of Kentucky Center of Excellence in Rural Health, Hazard, KY, USA |
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| Abstract: | Regular exercise has been shown to reduce the risk of Alzheimer's disease (AD).Our previous study showed that the protein aquaporin 4(AQP4),which is specificall... |
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| Keywords: | Alzheimer''s disease amyloid-beta astrocytes aquaporin-4 glymphatic system learning and memory synaptic protein transgenic mice voluntary exercise |
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