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

被引：168

作者：

Belarbi, Karim ^{[1
,2
,3
]}

Burnouf, Sylvie ^{[1
,2
,3
]}

Fernandez-Gomez, Francisco-Jose ^{[1
,2
]}

Laurent, Cyril ^{[1
,2
]}

Lestavel, Sophie ^{[1
,4
,5
]}

Figeac, Martin ^{[1
]}

Sultan, Audrey ^{[1
,2
]}

Troquier, Laetitia ^{[1
,2
]}

Leboucher, Antoine ^{[1
,2
]}

Caillierez, Raphaeelle ^{[1
,2
]}

Grosjean, Marie-Eve ^{[1
,2
]}

Demeyer, Dominique ^{[1
,2
]}

Obriot, Helene ^{[1
,2
]}

Brion, Ingrid ^{[1
]}

Barbot, Berangere ^{[1
,2
]}

Galas, Marie-Christine ^{[1
,2
]}

Staels, Bart ^{[1
,4
,5
]}

Humez, Sandrine ^{[1
,2
]}

Sergeant, Nicolas ^{[1
,2
,3
]}

Schraen-Maschke, Susanna ^{[1
,2
,3
]}

Muhr-Tailleux, Anne ^{[1
,4
,5
]}

Hamdane, Malika ^{[1
,2
]}

Buee, Luc ^{[1
,2
,3
]}

Blum, David ^{[1
,2
,3
]}

机构：

[1] Univ Lille Nord France, UDSL, F-59000 Lille, France

[2] INSERM, U837, Jean Pierre Aubert Res Ctr, F-59000 Lille, France

[3] CHRU, F-59000 Lille, France

[4] INSERM, U1011, F-59000 Lille, France

[5] Inst Pasteur, F-59000 Lille, France

来源：

NEUROBIOLOGY OF DISEASE | 2011年 / 43卷 / 02期

关键词：

Alzheimer's disease; Exercise; Tauopathies; THY-Tau22; Transgenic model; NPC1; PHYSICAL-ACTIVITY; SYNAPTIC PLASTICITY; NEUROTROPHIC FACTOR; GROWTH-FACTOR; NEUROFIBRILLARY TANGLES; MICROGLIAL ACTIVATION; COGNITIVE PERFORMANCE; MEMORY DEFICITS; SPATIAL MEMORY; BRAIN;

D O I：

10.1016/j.nbd.2011.04.022

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

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.

引用

页码：486 / 494

页数：9

共 80 条

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Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer's disease [J].