Beneficial effects of exercise in a transgenic mouse model of Alzheimer's disease-like Tau pathology

• Main Authors: Karim Belarbi, Sylvie Burnouf, Francisco-Jose Fernandez-Gomez, Cyril Laurent, Sophie Lestavel, Martin Figeac, Audrey Sultan, Laetitia Troquier, Antoine Leboucher, Raphaëlle Caillierez, Marie-Eve Grosjean, Dominique Demeyer, Hélène Obriot, Ingrid Brion, Bérangère Barbot, Marie-Christine Galas, Bart Staels, Sandrine Humez, Nicolas Sergeant, Susanna Schraen-Maschke, Anne Muhr-Tailleux, Malika Hamdane, Luc Buée, David Blum
• Format: Article
• Language: English
• Published: Elsevier 2011-08-01
• Series: Neurobiology of Disease
• Subjects: Alzheimer's disease; Exercise; Tauopathies; THY-Tau22; Transgenic model; NPC1
• Online Access: http://www.sciencedirect.com/science/article/pii/S0969996111001392

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.