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

Publication ,  Journal Article
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
Published in: Neurobiol Aging
July 2016

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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Published In

Neurobiol Aging

DOI

EISSN

1558-1497

Publication Date

July 2016

Volume

43

Start / End Page

47 / 57

Location

United States

Related Subject Headings

  • tau Proteins
  • Uncoupling Protein 1
  • Thermogenesis
  • Temperature
  • Synapses
  • Phosphorylation
  • Norepinephrine
  • Neurology & Neurosurgery
  • Mice, Transgenic
  • Energy Metabolism
 

Citation

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Chicago
ICMJE
MLA
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Vandal, M., White, P. J., Tournissac, M., Tremblay, C., St-Amour, I., Drouin-Ouellet, J., … Calon, F. (2016). Impaired thermoregulation and beneficial effects of thermoneutrality in the 3×Tg-AD model of Alzheimer's disease. Neurobiol Aging, 43, 47–57. https://doi.org/10.1016/j.neurobiolaging.2016.03.024
Vandal, Milene, Philip J. White, Marine Tournissac, Cyntia Tremblay, Isabelle St-Amour, Janelle Drouin-Ouellet, Melanie Bousquet, et al. “Impaired thermoregulation and beneficial effects of thermoneutrality in the 3×Tg-AD model of Alzheimer's disease.Neurobiol Aging 43 (July 2016): 47–57. https://doi.org/10.1016/j.neurobiolaging.2016.03.024.
Vandal M, White PJ, Tournissac M, Tremblay C, St-Amour I, Drouin-Ouellet J, et al. Impaired thermoregulation and beneficial effects of thermoneutrality in the 3×Tg-AD model of Alzheimer's disease. Neurobiol Aging. 2016 Jul;43:47–57.
Vandal, Milene, et al. “Impaired thermoregulation and beneficial effects of thermoneutrality in the 3×Tg-AD model of Alzheimer's disease.Neurobiol Aging, vol. 43, July 2016, pp. 47–57. Pubmed, doi:10.1016/j.neurobiolaging.2016.03.024.
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. Impaired thermoregulation and beneficial effects of thermoneutrality in the 3×Tg-AD model of Alzheimer's disease. Neurobiol Aging. 2016 Jul;43:47–57.
Journal cover image

Published In

Neurobiol Aging

DOI

EISSN

1558-1497

Publication Date

July 2016

Volume

43

Start / End Page

47 / 57

Location

United States

Related Subject Headings

  • tau Proteins
  • Uncoupling Protein 1
  • Thermogenesis
  • Temperature
  • Synapses
  • Phosphorylation
  • Norepinephrine
  • Neurology & Neurosurgery
  • Mice, Transgenic
  • Energy Metabolism