Impaired thermoregulation and beneficial effects of thermoneutrality in the 3×Tg-AD model of Alzheimer's disease
(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.
(Less)
- author
- organization
- publishing date
- 2016-07
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Journal Article
- in
- Neurobiology of Aging
- volume
- 43
- pages
- 11 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:27255814
- scopus:84964317452
- 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
- 2024-07-26 22:34:42
@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}}, }