Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/26906
Title: Dexmedetomidine directly increases tau phosphorylation
Authors: Huang, C
Ho, YS
Ng, OTW
Irwin, MG
Chang, RCC
Wong, GTC
Keywords: Anesthetics
Dexmedetomidine
Hypothermia
Protein kinases
Tau phosphorylation
Issue Date: 2015
Publisher: IOS Press
Source: Journal of alzheimer's disease, 2015, v. 44, no. 3, p. 839-850 How to cite?
Journal: Journal of alzheimer's disease 
Abstract: Exposure to anesthetic agents has been linked to abnormal tau protein phosphorylation, an antecedent to the development of neurofibrillary tangles. This study evaluates the direct and indirect effects of dexmedetomidine. Primary culture of cortical neurons established from Sprague-Dawley (SD) rat embryos were exposed to dexmedetomidine for 1 or 6 hours, and the degree of tau phosphorylation at the AT8, AT180, and S396 sites was assessed by western blot analysis. To assess and compare their relative in vivo effects, the same agent was administered intravenously to 8 to 10 week old male SD rats and titrated to the loss of the righting reflex for 2 hours. After 1 hour of recovery, the rats were sacrificed and samples taken from the cortex and hippocampus were subjected to western blot and immunohistochemical analysis. The in vitro studies reviewed significant hyperphosphorylation only at the S396 site, and these changes have largely disappeared at 6 hours. With temperature maintenance, dexmedetomidine induced significant changes in hyperphosphorylation at the AT8 site in the cortex and hippocampus and at the AT180 in the hippocampus. The direct effect of anesthetic agents on fully differentiated cortical neurons is epitope-specific and short-lived. The in vivo effects are comparatively more complicated and depend not only on the phosphorylation site but the regions of the brain examined. These findings suggest that dexmedetomidine increases tau phosphorylation both in vitro and in vivo under normothermic conditions, and further studies are warranted to determine the long-term impact of this anesthetic on the tau pathology and even cognitive function.
URI: http://hdl.handle.net/10397/26906
ISSN: 1387-2877
EISSN: 1875-8908
DOI: 10.3233/JAD-142238
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