|Title||Impaired thermoregulation and beneficial effects of thermoneutrality in the 3×Tg-AD model of Alzheimer's disease.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Auteurs||Vandal, M, White, PJ, Tournissac, M, Tremblay, C, St-Amour, I, Drouin-Ouellet, J, Bousquet, M, Traversy, M-T, Planel, E, Marette, A, Calon, F|
|Date Published||2016 Jul|
|Keywords||Adipose 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|
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.
|Alternate Journal||Neurobiol. Aging|