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

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• 作者：Milene Vandal^a ; ^b ; ^c ; Philip J. White^d ; ^e ; ^f ; Marine Tournissac^a ; ^b ; ^c ; Cyntia Tremblay^b ; Isabelle St-Amour^a ; ^b ; ^g ; Janelle Drouin-Ouellet^e ; ^h ; Melanie Bousquet^a ; ^b ; ^c ; Marie-Thé ; rè ; se Traversy^a ; ^b ; Emmanuel Planel^b ; ^e ; Andre Marette^c ; ^e ; ^f ; Frederic Calon^a ; ^b ; ^c ; ^{frederic.calon@pha.ulaval.ca" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Alzheimer's disease ; Thermogenesis ; Cold exposure ; Thermoneutrality ; 3× ; Tg-AD
• 刊名：Neurobiology of Aging
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：43
• 期：Complete
• 页码：47-57
• 全文大小：1011 K

文摘

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.