دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Hypothermia mediates age-dependent increase of tau phosphorylation in db/db mice.
المؤلفون: El Khoury NB; Université Laval, Faculté de Médecine, Département de Psychiatrie et Neurosciences, Québec, QC, Canada; Centre de recherche du Centre Hospitalier de l'Université Laval de Québec, Axe Neurosciences, Québec, QC, Canada., Gratuze M; Université Laval, Faculté de Médecine, Département de Psychiatrie et Neurosciences, Québec, QC, Canada; Centre de recherche du Centre Hospitalier de l'Université Laval de Québec, Axe Neurosciences, Québec, QC, Canada., Petry F; Université Laval, Faculté de Médecine, Département de Psychiatrie et Neurosciences, Québec, QC, Canada; Centre de recherche du Centre Hospitalier de l'Université Laval de Québec, Axe Neurosciences, Québec, QC, Canada., Papon MA; Centre de recherche du Centre Hospitalier de l'Université Laval de Québec, Axe Neurosciences, Québec, QC, Canada., Julien C; Centre de recherche du Centre Hospitalier de l'Université Laval de Québec, Axe Neurosciences, Québec, QC, Canada., Marcouiller F; Université Laval, Faculté de Médecine, Département de Psychiatrie et Neurosciences, Québec, QC, Canada; Centre de recherche du Centre Hospitalier de l'Université Laval de Québec, Axe Neurosciences, Québec, QC, Canada., Morin F; Centre de recherche du Centre Hospitalier de l'Université Laval de Québec, Axe Neurosciences, Québec, QC, Canada., Nicholls SB; MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Alzheimer's Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA., Calon F; Centre de recherche du Centre Hospitalier de l'Université Laval de Québec, Axe Neurosciences, Québec, QC, Canada; Université Laval, Faculté de Pharmacie, Québec, Canada., Hébert SS; Université Laval, Faculté de Médecine, Département de Psychiatrie et Neurosciences, Québec, QC, Canada; Centre de recherche du Centre Hospitalier de l'Université Laval de Québec, Axe Neurosciences, Québec, QC, Canada., Marette A; Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, Canada., Planel E; Université Laval, Faculté de Médecine, Département de Psychiatrie et Neurosciences, Québec, QC, Canada; Centre de recherche du Centre Hospitalier de l'Université Laval de Québec, Axe Neurosciences, Québec, QC, Canada. Electronic address: emmanuel@planel.org.
المصدر: Neurobiology of disease [Neurobiol Dis] 2016 Apr; Vol. 88, pp. 55-65. Date of Electronic Publication: 2016 Jan 09.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Academic Press Country of Publication: United States NLM ID: 9500169 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-953X (Electronic) Linking ISSN: 09699961 NLM ISO Abbreviation: Neurobiol Dis Subsets: MEDLINE
أسماء مطبوعة: Publication: San Diego, CA : Academic Press
Original Publication: Oxford : Blackwell Science, c1994-
مواضيع طبية MeSH: Hypothermia, Induced*, Aging/*physiology , Diabetes Mellitus, Type 2/*therapy , tau Proteins/*metabolism, Analysis of Variance ; Animals ; Blood Glucose ; Body Weight/genetics ; Body Weight/physiology ; Brain/metabolism ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/pathology ; Disease Models, Animal ; Gene Expression Regulation/genetics ; Glycemic Index ; Insulin Resistance/genetics ; Leptin/deficiency ; Leptin/genetics ; MAP Kinase Kinase 4/metabolism ; Male ; Mice ; Mice, Mutant Strains ; Phosphorylation/genetics ; Signal Transduction/genetics
مستخلص: 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.
(Copyright © 2016 Elsevier Inc. All rights reserved.)
معلومات مُعتمدة: Canada Canadian Institutes of Health Research
فهرسة مساهمة: Keywords: Alzheimer's disease; Diabetes mellitus; Hippocampus; Hypothermia; Kinase; Phosphatase; Tau hyperphosphorylation; Temperature; Thermoregulation; db/db mice
المشرفين على المادة: 0 (Blood Glucose)
0 (Leptin)
0 (tau Proteins)
EC 2.7.12.2 (MAP Kinase Kinase 4)
تواريخ الأحداث: Date Created: 20160119 Date Completed: 20161213 Latest Revision: 20161230
رمز التحديث: 20231215
DOI: 10.1016/j.nbd.2016.01.005
PMID: 26777665
قاعدة البيانات: MEDLINE
الوصف
تدمد:1095-953X
DOI:10.1016/j.nbd.2016.01.005