title: Beneficial effects of exercise in a transgenic mouse model of Alzheimer's disease-like Tau pathology.
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.
authors.affiliation: Université Lille-Nord de France, UDSL, F-59000 Lille, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Belarbi
authors.forename: Sylvie
authors.initials: S
authors.lastname: Burnouf
authors.forename: Francisco-Jose
authors.initials: FJ
authors.lastname: Fernandez-Gomez
authors.forename: Cyril
authors.initials: C
authors.lastname: Laurent
authors.forename: Sophie
authors.initials: S
authors.lastname: Lestavel
authors.forename: Martin
authors.initials: M
authors.lastname: Figeac
authors.forename: Audrey
authors.initials: A
authors.lastname: Sultan
authors.forename: Laetitia
authors.initials: L
authors.lastname: Troquier
authors.forename: Antoine
authors.initials: A
authors.lastname: Leboucher
authors.forename: Raphaëlle
authors.initials: R
authors.lastname: Caillierez
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Grosjean
authors.forename: Dominique
authors.initials: D
authors.lastname: Demeyer
authors.forename: Hélène
authors.initials: H
authors.lastname: Obriot
authors.forename: Ingrid
authors.initials: I
authors.lastname: Brion
authors.forename: Bérangère
authors.initials: B
authors.lastname: Barbot
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Galas
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: Sandrine
authors.initials: S
authors.lastname: Humez
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sergeant
authors.forename: Susanna
authors.initials: S
authors.lastname: Schraen-Maschke
authors.forename: Anne
authors.initials: A
authors.lastname: Muhr-Tailleux
authors.forename: Malika
authors.initials: M
authors.lastname: Hamdane
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
authors.forename: David
authors.initials: D
authors.lastname: Blum
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D004195:Disease Models, Animal; D005081:Exercise Therapy / Q000379:methods*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010805:Physical Conditioning, Animal / Q000502:physiology*; D016875:tau Proteins / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D016875:tau Proteins