Repeated cold exposures protect a mouse model of Alzheimer's disease against cold-induced tau phosphorylation
| Autor: | Sébastien S. Hébert, Ruben D. Martinez-Cano, Philippe Bourassa, Frédéric Calon, Emmanuel Planel, Marine Tournissac, Tra-My Vu |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
lcsh:Internal medicine medicine.medical_specialty FGF21 Hippocampus Mice Transgenic tau Proteins 030209 endocrinology & metabolism Stimulation Neuropathology Mice 03 medical and health sciences 0302 clinical medicine Alzheimer Disease Internal medicine Brown adipose tissue medicine Animals 3xTg-AD mice Phosphorylation lcsh:RC31-1245 Molecular Biology thermoregulation business.industry tau phosphorylation brown adipose tissue Cell Biology Alzheimer's disease Glucose Tolerance Test Hypothermia Thermoregulation Cold Temperature Disease Models Animal 030104 developmental biology Endocrinology medicine.anatomical_structure Original Article medicine.symptom business Thermogenesis |
| Zdroj: | Molecular Metabolism, Vol 22, Iss, Pp 110-120 (2019) Molecular Metabolism |
| ISSN: | 2212-8778 |
| Popis: | Objective Old age is associated with a rise in the incidence of Alzheimer's disease (AD) but also with thermoregulatory deficits. Indicative of a link between the two, hypothermia induces tau hyperphosphorylation. The 3xTg-AD mouse model not only develops tau and amyloid pathologies in the brain but also metabolic and thermoregulatory deficits. Brown adipose tissue (BAT) is the main thermogenic driver in mammals, and its stimulation counteracts metabolic deficits in rodents and humans. We thus investigated whether BAT stimulation impedes AD neuropathology. Methods 15-month-old 3xTg-AD mice were subjected to repeated short cold exposures (RSCE), consisting of 4-hour sessions of cold exposure (4 °C), five times per week for four weeks, compared to animals kept at housing temperature. Results First, we confirmed that 3xTg-AD RSCE-trained mice exhibited BAT thermogenesis and improved glucose tolerance. RSCE-trained mice were completely resistant to tau hyperphosphorylation in the hippocampus induced by a 24-hour cold challenge. Finally, RSCE increased plasma levels of fibroblast growth factor 21 (FGF21), a batokine, which inversely correlated with hippocampal tau phosphorylation. Conclusions Overall, BAT stimulation through RSCE improved metabolic deficits and completely blocked cold-induced tau hyperphosphorylation in the 3xTg-AD mouse model of AD neuropathology. These results suggest that improving thermogenesis could exert a therapeutic effect in AD. Highlights • Cold acclimation increases brown adipose tissue thermogenesis in old 3xTg-AD mice. • Cold acclimation improved glucose tolerance in old 3xTg-AD mice. • Enhanced thermogenesis protects against cold-induced brain tau phosphorylation. • Repeated cold exposures increased plasmatic levels of fibroblast growth factor 21. • Peripheral fibroblast growth factor 21 levels correlate with tau phosphorylation. |
| Databáze: | OpenAIRE |
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