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Targeting hyperphosphorylated tau with sodium selenate suppresses seizures in rodent models.
- Source :
-
Neurobiology of disease [Neurobiol Dis] 2012 Mar; Vol. 45 (3), pp. 897-901. Date of Electronic Publication: 2011 Dec 11. - Publication Year :
- 2012
-
Abstract
- Tau hyperphosphorylation has been implicated in the pathogenesis of a variety of forms of human epilepsy. Here we investigated whether treatment with sodium selenate, a drug which reduces pathological hyperphosphorylated tau by enhancement of PP2A activity, would inhibit seizures in rodent models. In vitro, sodium selenate reduced tau phosphorylation in human neuroblastoma cells and reversed the increase in tau phosphorylation induced by the PP2A inhibitor, okadaic acid. Sodium selenate treatment was then tested against three different rodent seizure models. Firstly the propensity of 6-Hz electrical corneal stimulation to induce seizures in adult mice was assessed following acute treatment with different doses of sodium selenate. Secondly, the number of seizures induced by pentylenetetrazole (PTZ) was quantified in rats following chronic sodium selenate treatment via drinking water. Finally, amygdala kindled rats were chronically treated with sodium selenate in drinking water and the length and the severity of the seizures evoked by stimulation of the amygdala recorded. The results demonstrated a dose-dependent protection of sodium selenate against 6-Hz stimulation induced seizures, and significant reduction in the total number of seizures following PTZ injection. Amygdala kindled rats chronically treated with sodium selenate had significantly shorter seizure duration compared controls, with more pronounced effects observed as the duration of treatment increased. The results of this study indicate that targeting hyperphosphorylated tau by treatment with sodium selenate has anti-seizure effects in a broad range of rodent models, and may represent a novel approach to treatment of patients with epilepsy.<br /> (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Subjects :
- Amygdala drug effects
Amygdala metabolism
Analysis of Variance
Animals
Cell Line, Tumor
Convulsants adverse effects
Disease Models, Animal
Dose-Response Relationship, Drug
Electric Stimulation adverse effects
Enzyme Inhibitors pharmacology
Gene Expression Regulation drug effects
Gene Expression Regulation genetics
Humans
Leucine genetics
Male
Mutation genetics
Neuroblastoma
Okadaic Acid pharmacology
Pentylenetetrazole adverse effects
Phosphorylation drug effects
Proline genetics
Rats
Rats, Sprague-Dawley
Rats, Wistar
Seizures etiology
Selenic Acid
Time Factors
Transfection
tau Proteins genetics
Antioxidants therapeutic use
Seizures drug therapy
Selenium Compounds therapeutic use
tau Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1095-953X
- Volume :
- 45
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Neurobiology of disease
- Publication Type :
- Academic Journal
- Accession number :
- 22182692
- Full Text :
- https://doi.org/10.1016/j.nbd.2011.12.005