Hypothermia mediates age-dependent increase of tau phosphorylation in db/db mice

Neurobiology of Disease
Noura B El KhouryEmmanuel Planel

Abstract

Accumulating evidence from epidemiological studies suggest that type 2 diabetes is linked to an increased risk of Alzheimer's disease (AD). However, the consequences of type 2 diabetes on AD pathologies, such as tau hyperphosphorylation, are not well understood. Here, we evaluated the impact of type 2 diabetes on tau phosphorylation in db/db diabetic mice aged 4 and 26weeks. We found increased tau phosphorylation at the CP13 epitope correlating with a deregulation of c-Jun. N-terminal kinase (JNK) and Protein Phosphatase 2A (PP2A) in 4-week-old db/db mice. 26-week-old db/db mice displayed tau hyperphosphorylation at multiple epitopes (CP13, AT8, PHF-1), but no obvious change in kinases or phosphatases, no cleavage of tau, and no deregulation of central insulin signaling pathways. In contrast to younger animals, 26-week-old db/db mice were hypothermic and restoration of normothermia rescued phosphorylation at most epitopes. Our results suggest that, at early stages of type 2 diabetes, changes in tau phosphorylation may be due to deregulation of JNK and PP2A, while at later stages hyperphosphorylation is mostly a consequence of hypothermia. These results provide a novel link between diabetes and tau pathology, and underlie the im...Continue Reading

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Citations

Nov 27, 2018·The Journal of Endocrinology·Lenka MaletínskáJaroslav Kuneš
Mar 14, 2020·Clinical Science·Miroslava KacířováLenka Maletínská
Dec 10, 2016·Frontiers in Cellular Neuroscience·Chang-Qing LiQing-Ping Zeng
Feb 26, 2019·Frontiers in Cellular Neuroscience·Rafaella Araujo GonçalvesFernanda G De Felice
Jun 23, 2019·Journal of Alzheimer's Disease : JAD·Elizabeth Kurudamannil George, P Hemachandra Reddy
Aug 19, 2017·Scientific Reports·Ambika KrishnankuttyShin-Ichi Hisanaga
Jan 29, 2019·Journal of Alzheimer's Disease : JAD·Veronika PražienkováLenka Maletínská
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Oct 30, 2020·Frontiers in Neurology·Emmanuelle BoscherSébastien S Hébert
May 30, 2017·Neurochemistry International·Mitsuru Shinohara, Naoyuki Sato

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