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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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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Journal Article
in
Neurobiology of Aging
volume
43
pages
11 pages
publisher
Elsevier
external identifiers
  • scopus:84964317452
  • pmid:27255814
ISSN
1558-1497
DOI
10.1016/j.neurobiolaging.2016.03.024
language
English
LU publication?
no
id
b152c44a-6fe2-4526-8c9c-5ad54f6140c2
date added to LUP
2016-11-22 08:56:18
date last changed
2024-06-01 20:10:50
@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}},
  keywords     = {{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}},
  doi          = {{10.1016/j.neurobiolaging.2016.03.024}},
  volume       = {{43}},
  year         = {{2016}},
}