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

Vandal, Milene; White, Philip J; Tournissac, Marine; Tremblay, Cyntia; St-Amour, Isabelle; Drouin-Ouellet, Janelle LU ; Bousquet, Melanie; Traversy, Marie-Thérèse; Planel, Emmanuel and Marette, Andre, et al. (2016) In Neurobiology of Aging 43. p.47-57
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... (More)

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.

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keywords
Journal Article
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Neurobiology of Aging
volume
43
pages
11 pages
publisher
Elsevier
external identifiers
  • scopus:84964317452
ISSN
1558-1497
DOI
10.1016/j.neurobiolaging.2016.03.024
language
English
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no
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b152c44a-6fe2-4526-8c9c-5ad54f6140c2
date added to LUP
2016-11-22 08:56:18
date last changed
2017-06-25 04:56:13
@article{b152c44a-6fe2-4526-8c9c-5ad54f6140c2,
  abstract     = {<p>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.</p>},
  author       = {Vandal, Milene and White, Philip J and Tournissac, Marine and Tremblay, Cyntia and St-Amour, Isabelle and Drouin-Ouellet, Janelle and Bousquet, Melanie and Traversy, Marie-Thérèse and Planel, Emmanuel and Marette, Andre and Calon, Frederic},
  issn         = {1558-1497},
  keyword      = {Journal Article},
  language     = {eng},
  pages        = {47--57},
  publisher    = {Elsevier},
  series       = {Neurobiology of Aging},
  title        = {Impaired thermoregulation and beneficial effects of thermoneutrality in the 3×Tg-AD model of Alzheimer's disease},
  url          = {http://dx.doi.org/10.1016/j.neurobiolaging.2016.03.024},
  volume       = {43},
  year         = {2016},
}