دورية أكاديمية
أعرض في EDS

Dexmedetomidine increases tau phosphorylation under normothermic conditions in vivo and in vitro.

التفاصيل البيبلوغرافية
العنوان: Dexmedetomidine increases tau phosphorylation under normothermic conditions in vivo and in vitro.
المؤلفون: Whittington RA; Department of Anesthesiology, Columbia University, College of Physicians and Surgeons, New York, NY, USA. Electronic address: raw9@cumc.columbia.edu., Virág L; Department of Anesthesiology, Columbia University, College of Physicians and Surgeons, New York, NY, USA., Gratuze M; Département de Psychiatrie et Neurosciences, Faculté de Médecine, Université Laval, Québec, Québec, Canada., Petry FR; Département de Psychiatrie et Neurosciences, Faculté de Médecine, Université Laval, Québec, Québec, Canada., Noël A; Département de Psychiatrie et Neurosciences, Faculté de Médecine, Université Laval, Québec, Québec, Canada., Poitras I; Département de Psychiatrie et Neurosciences, Faculté de Médecine, Université Laval, Québec, Québec, Canada., Truchetti G; Département de Psychiatrie et Neurosciences, Faculté de Médecine, Université Laval, Québec, Québec, Canada., Marcouiller F; Département de Psychiatrie et Neurosciences, Faculté de Médecine, Université Laval, Québec, Québec, Canada., Papon MA; Département de Psychiatrie et Neurosciences, Faculté de Médecine, Université Laval, Québec, Québec, Canada., El Khoury N; Département de Psychiatrie et Neurosciences, Faculté de Médecine, Université Laval, Québec, Québec, Canada., Wong K; Department of Anesthesiology, Columbia University, College of Physicians and Surgeons, New York, NY, USA., Bretteville A; Département de Psychiatrie et Neurosciences, Faculté de Médecine, Université Laval, Québec, Québec, Canada., Morin F; Neurosciences, CHUL, CRCHU, Québec, Québec, Canada., Planel E; Département de Psychiatrie et Neurosciences, Faculté de Médecine, Université Laval, Québec, Québec, Canada; Neurosciences, CHUL, CRCHU, Québec, Québec, Canada.
المصدر: Neurobiology of aging [Neurobiol Aging] 2015 Aug; Vol. 36 (8), pp. 2414-28. Date of Electronic Publication: 2015 May 09.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 8100437 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1558-1497 (Electronic) Linking ISSN: 01974580 NLM ISO Abbreviation: Neurobiol Aging Subsets: MEDLINE
أسماء مطبوعة: Publication: New York : Elsevier
Original Publication: Fayetteville, N.Y. : Ankho International.
مواضيع طبية MeSH: Dexmedetomidine/*adverse effects , Hypnotics and Sedatives/*adverse effects , tau Proteins/*metabolism, Adrenergic alpha-2 Receptor Antagonists/pharmacology ; Animals ; Cells, Cultured ; Dexmedetomidine/administration & dosage ; Dexmedetomidine/antagonists & inhibitors ; Dose-Response Relationship, Drug ; Hippocampus/metabolism ; Humans ; Hypnotics and Sedatives/administration & dosage ; Hypothermia, Induced ; In Vitro Techniques ; Infusions, Intravenous ; Mice, Inbred C57BL ; Phosphorylation/drug effects ; Protein Aggregation, Pathological/chemically induced ; Spatial Memory/drug effects
مستخلص: There is developing interest in the potential association between anesthesia and the onset and progression of Alzheimer's disease. Several anesthetics have, thus, been demonstrated to induce tau hyperphosphorylation, an effect mostly mediated by anesthesia-induced hypothermia. Here, we tested the hypothesis that acute normothermic administration of dexmedetomidine (Dex), an intravenous sedative used in intensive care units, would result in tau hyperphosphorylation in vivo and in vitro. When administered to nontransgenic mice, Dex-induced tau hyperphosphorylation persisting up to 6 hours in the hippocampus for the AT8 epitope. Pretreatment with atipamezole, a highly specific α2-adrenergic receptor antagonist, blocked Dex-induced tau hyperphosphorylation. Furthermore, Dex dose-dependently increased tau phosphorylation at AT8 in SH-SY5Y cells, impaired mice spatial memory in the Barnes maze and promoted tau hyperphosphorylation and aggregation in transgenic hTau mice. These findings suggest that Dex: (1) increases tau phosphorylation, in vivo and in vitro, in the absence of anesthetic-induced hypothermia and through α2-adrenergic receptor activation, (2) promotes tau aggregation in a mouse model of tauopathy, and (3) impacts spatial reference memory.
(Copyright © 2015 Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: R01 GM101698 United States GM NIGMS NIH HHS; MOP-106423 Canada Canadian Institutes of Health Research; PCN-102993 Canada Canadian Institutes of Health Research; R01GM101698 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: Alzheimer's disease; Anesthesia; Cells; Dexmedetomidine; Mouse; Tau
المشرفين على المادة: 0 (Adrenergic alpha-2 Receptor Antagonists)
0 (Hypnotics and Sedatives)
0 (tau Proteins)
67VB76HONO (Dexmedetomidine)
تواريخ الأحداث: Date Created: 20150611 Date Completed: 20160317 Latest Revision: 20181113
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC4465078
DOI: 10.1016/j.neurobiolaging.2015.05.002
PMID: 26058840
قاعدة البيانات: MEDLINE
الوصف
تدمد:1558-1497
DOI:10.1016/j.neurobiolaging.2015.05.002