Impaired thermoregulation and beneficial effects of thermoneutrality in the 3×Tg-AD model of Alzheimer's disease.

TitleImpaired thermoregulation and beneficial effects of thermoneutrality in the 3×Tg-AD model of Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2016
AuthorsVandal, M, White, PJ, Tournissac, M, Tremblay, C, St-Amour, I, Drouin-Ouellet, J, Bousquet, M, Traversy, M-T, Planel, E, Marette, A, Calon, F
JournalNeurobiol Aging
Volume43
Pagination47-57
Date Published2016 Jul
ISSN1558-1497
KeywordsAdipose Tissue, Brown, Alzheimer Disease, Amyloid beta-Peptides, Animals, Body Temperature, Body Temperature Regulation, Cold Temperature, Disease Models, Animal, Energy Metabolism, Mice, Transgenic, Norepinephrine, Phosphorylation, Synapses, tau Proteins, Temperature, Thermogenesis, Uncoupling Protein 1
Abstract

The sharp rise in the incidence of Alzheimer's disease (AD) at an old age coincides with a reduction in energy metabolism and core body temperature. We found that the triple-transgenic mouse model of AD (3×Tg-AD) spontaneously develops a lower basal body temperature and is more vulnerable to a cold environment compared with age-matched controls. This was despite higher nonshivering thermogenic activity, as evidenced by brown adipose tissue norepinephrine content and uncoupling protein 1 expression. A 24-hour exposure to cold (4 °C) aggravated key neuropathologic markers of AD such as: tau phosphorylation, soluble amyloid beta concentrations, and synaptic protein loss in the cortex of 3×Tg-AD mice. Strikingly, raising the body temperature of aged 3×Tg-AD mice via exposure to a thermoneutral environment improved memory function and reduced amyloid and synaptic pathologies within a week. Our results suggest the presence of a vicious cycle between impaired thermoregulation and AD-like neuropathology, and it is proposed that correcting thermoregulatory deficits might be therapeutic in AD.

DOI10.1016/j.neurobiolaging.2016.03.024
Alternate JournalNeurobiol. Aging
PubMed ID27255814