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Prog Neuropsychopharmacol Biol Psychiatry. 2017 Oct 3;79(Pt B):452-461. doi: 10.1016/j.pnpbp.2017.08.001. Epub 2017 Aug 3.

Differential effects of voluntary treadmill exercise and caloric restriction on tau pathogenesis in a mouse model of Alzheimer's disease-like tau pathology fed with Western diet.

Author information

1
Université Laval, Faculté de médecine, Département de Psychiatrie et Neurosciences, Québec, Canada; Centre de Recherche du CHU de Québec, Axe Neurosciences, Québec, Canada. Electronic address: maudgratuze@gmail.com.
2
Centre de Recherche du CHU de Québec, Axe Neurosciences, Québec, Canada. Electronic address: jacinthe.julien@crchudequebec.ulaval.ca.
3
Centre de Recherche du CHU de Québec, Axe Neurosciences, Québec, Canada. Electronic address: Francoise.Morin@crchul.ulaval.ca.
4
Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Canada. Electronic address: andre.marette@criucpq.ulaval.ca.
5
Université Laval, Faculté de médecine, Département de Psychiatrie et Neurosciences, Québec, Canada; Centre de Recherche du CHU de Québec, Axe Neurosciences, Québec, Canada. Electronic address: emmanuel@planel.org.

Abstract

BACKGROUND:

Tau is a microtubule-associated protein that becomes pathological when it undergoes hyperphosphorylation and aggregation as seen in Alzheimer's disease (AD). AD is mostly sporadic, with environmental, biological and/or genetic risks factors, interacting together to promote the disease. In the past decade, reports have suggested that obesity in midlife could be one of these risk factors. On the other hand, caloric restriction and physical exercise have been reported to reduce the incidence and outcome of obesity as well as AD.

METHODS:

We evaluated the impact of voluntary physical exercise and caloric restriction on tau pathology during 2months in hTau mice under high caloric diet in order to evaluate if these strategies could prevent AD-like pathology in obese conditions.

RESULTS:

We found no effects of obesity induced by Western diet on both Tau phosphorylation and aggregation compared to controls. However, exercise reduced tau phosphorylation while caloric restriction exacerbated its aggregation in the brains of obese hTau mice. We then examined the mechanisms underlying changes in tau phosphorylation and aggregation by exploring major tau kinases and phosphatases and key proteins involved in autophagy. However, there were no significant effects of voluntary exercise and caloric restriction on these proteins in hTau mice that could explain our results.

CONCLUSION:

In this study, we report differential effects of voluntary treadmill exercise and caloric restriction on tau pathogenesis in our obese mice, namely beneficial effect of exercise on tau phosphorylation and deleterious effect of caloric restriction on tau aggregation. Our results suggest that lifestyle strategies used to reduce metabolic disorders and AD must be selected and studied carefully to avoid exacerbation of pathologies.

KEYWORDS:

Alzheimer's disease; Caloric restriction; Exercise; Obesity; Tau pathology; Tau phosphorylation; Tauopathies; Western diet

PMID:
28779908
DOI:
10.1016/j.pnpbp.2017.08.001
[Indexed for MEDLINE]

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