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Beneficial effects of exercise in a transgenic mouse model of Alzheimer's disease-like Tau pathology.
- Source :
-
Neurobiology of disease [Neurobiol Dis] 2011 Aug; Vol. 43 (2), pp. 486-94. Date of Electronic Publication: 2011 May 04. - Publication Year :
- 2011
-
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.<br /> (Copyright © 2011 Elsevier Inc. All rights reserved.)
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1095-953X
- Volume :
- 43
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Neurobiology of disease
- Publication Type :
- Academic Journal
- Accession number :
- 21569847
- Full Text :
- https://doi.org/10.1016/j.nbd.2011.04.022