期刊
NEUROBIOLOGY OF DISEASE
卷 43, 期 2, 页码 486-494出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2011.04.022
关键词
Alzheimer's disease; Exercise; Tauopathies; THY-Tau22; Transgenic model; NPC1
资金
- Inserm
- CNRS
- DN2M
- FEDER
- IMPRT
- University of Lille 2
- Lille Regional Hospital (CHRU)
- Region Nord/Pas-de-Calais
- Fondation Cceur Arteres
- LECMA
- MEDIALZ
- ANR
- European Community [200611]
- CHRU
- Communidad Castilla-La-Mancha
- French Research Ministry
Tau pathology is encountered in many neurodegenerative disorders known as tauopathies, including Alzheimer's disease. Physical activity is a lifestyle factor affecting processes crucial for memory and synaptic plasticity. Whether long-term voluntary exercise has an impact on Tau pathology and its pathophysiological consequences is currently unknown. To address this question, we investigated the effects of long-term voluntary exercise in the THY-Tau22 transgenic model of Alzheimer's disease-like Tau pathology, characterized by the progressive development of Tau pathology, cholinergic alterations and subsequent memory impairments. Three-month-old THY-Tau22 mice and wild-type littermates were assigned to standard housing or housing supplemented with a running wheel. After 9 months of exercise, mice were evaluated for memory performance and examined for hippocampal Tau pathology, cholinergic defects, inflammation and genes related to cholesterol metabolism. Exercise prevented memory alterations in THY-Tau22 mice. This was accompanied by a decrease in hippocampal Tau pathology and a prevention of the loss of expression of choline acetyltransferase within the medial septum. Whereas the expression of most cholesterol-related genes remained unchanged in the hippocampus of running THY-Tau22 mice, we observed a significant upregulation in mRNA levels of NPC1 and NPC2, genes involved in cholesterol trafficking from the lysosomes. Our data support the view that long-term voluntary physical exercise is an effective strategy capable of mitigating Tau pathology and its pathophysiological consequences. (C) 2011 Elsevier Inc. All rights reserved.
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