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

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...

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Bibliographic Details
Published in:Neurobiology of aging 2016-07, Vol.43, p.47-57
Main Authors: Vandal, Milene, White, Philip J., Tournissac, Marine, Tremblay, Cyntia, St-Amour, Isabelle, Drouin-Ouellet, Janelle, Bousquet, Melanie, Traversy, Marie-Thérèse, Planel, Emmanuel, Marette, Andre, Calon, Frederic
Format: Article
Language:English
Subjects:
3×Tg-AD
Adipose Tissue, Brown - metabolism
Alzheimer Disease - etiology
Alzheimer Disease - metabolism
Alzheimer Disease - physiopathology
Alzheimer Disease - therapy
Alzheimer's disease
Amyloid beta-Peptides - metabolism
Animals
Body Temperature - physiology
Body Temperature Regulation
Cold exposure
Cold Temperature - adverse effects
Disease Models, Animal
Energy Metabolism - physiology
Mice, Transgenic
Norepinephrine - metabolism
Phosphorylation
Synapses - pathology
tau Proteins - metabolism
Temperature
Thermogenesis
Thermogenesis - physiology
Thermoneutrality
Uncoupling Protein 1 - metabolism
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Summary: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.
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2016.03.024