Intracerebroventricular administration of okadaic acid induces hippocampal glucose uptake dysfunction and tau phosphorylation.

Autor: Broetto N; Neuroscience Post-Graduation Program, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Hansen F; Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Brolese G; Neuroscience Post-Graduation Program, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Batassini C; Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Lirio F; Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Galland F; Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Dos Santos JP; Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Dutra MF; Department of Cellular Biology, Embryology and Genetics, Universidade Federal de Santa Catarina, Florianópolis, Brazil., Gonçalves CA; Neuroscience Post-Graduation Program, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. Electronic address: casg@ufrgs.br.
Jazyk: angličtina
Zdroj: Brain research bulletin [Brain Res Bull] 2016 Jun; Vol. 124, pp. 136-43. Date of Electronic Publication: 2016 Apr 21.
DOI: 10.1016/j.brainresbull.2016.04.014
Abstrakt: Intraneuronal aggregates of neurofibrillary tangles (NFTs), together with beta-amyloid plaques and astrogliosis, are histological markers of Alzheimer's disease (AD). The underlying mechanism of sporadic AD remains poorly understood, but abnormal hyperphosphorylation of tau protein is suggested to have a role in NFTs genesis, which leads to neuronal dysfunction and death. Okadaic acid (OKA), a strong inhibitor of protein phosphatase 2A, has been used to induce dementia similar to AD in rats. We herein investigated the effect of intracerebroventricular (ICV) infusion of OKA (100 and 200ng) on hippocampal tau phosphorylation at Ser396, which is considered an important fibrillogenic tau protein site, and on glucose uptake, which is reduced early in AD. ICV infusion of OKA (at 200ng) induced a spatial cognitive deficit, hippocampal astrogliosis (based on GFAP increment) and increase in tau phosphorylation at site 396 in this model. Moreover, we observed a decreased glucose uptake in the hippocampal slices of OKA-treated rats. In vitro exposure of hippocampal slices to OKA altered tau phosphorylation at site 396, without any associated change in glucose uptake activity. Taken together, these findings further our understanding of OKA neurotoxicity, in vivo and vitro, particularly with regard to the role of tau phosphorylation, and reinforce the importance of the OKA dementia model for studying the neurochemical alterations that may occur in AD, such as NFTs and glucose hypometabolism.
(Copyright © 2016 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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