1. Beneficial effects of exercise in a transgenic mouse model of Alzheimer's disease-like Tau pathology.
- Author
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Belarbi K, Burnouf S, Fernandez-Gomez FJ, Laurent C, Lestavel S, Figeac M, Sultan A, Troquier L, Leboucher A, Caillierez R, Grosjean ME, Demeyer D, Obriot H, Brion I, Barbot B, Galas MC, Staels B, Humez S, Sergeant N, Schraen-Maschke S, Muhr-Tailleux A, Hamdane M, Buée L, and Blum D
- Subjects
- Alzheimer Disease physiopathology, Animals, Disease Models, Animal, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, tau Proteins adverse effects, tau Proteins antagonists & inhibitors, Alzheimer Disease pathology, Alzheimer Disease therapy, Exercise Therapy methods, Physical Conditioning, Animal physiology, tau Proteins genetics
- Abstract
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., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
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