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

TitleHypothermia mediates age-dependent increase of tau phosphorylation in db/db mice.
Publication TypeJournal Article
Year of Publication2016
AuteursKhoury, NBEl, Gratuze, M, Petry, F, Papon, M-A, Julien, C, Marcouiller, F, Morin, F, Nicholls, SB, Calon, F, Hébert, SS, Marette, A, Planel, E
JournalNeurobiol Dis
Volume88
Pagination55-65
Date Published2016 Apr
ISSN1095-953X
KeywordsAging, Analysis of Variance, Animals, Blood Glucose, Body Weight, Brain, Diabetes Mellitus, Type 2, Disease Models, Animal, Gene Expression Regulation, Glycemic Index, Hypothermia, Induced, Insulin Resistance, Leptin, Male, MAP Kinase Kinase 4, Mice, Mice, Mutant Strains, Phosphorylation, Signal Transduction, tau Proteins
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 importance of recording body temperature to better understand the relationship between diabetes and AD.

DOI10.1016/j.nbd.2016.01.005
Alternate JournalNeurobiol. Dis.
PubMed ID26777665
Grant List / / Canadian Institutes of Health Research / Canada