Long-Term Valproate Treatment Increases Brain Neuropeptide Y Expression and Decreases Seizure Expression in a Genetic Rat Model of Absence Epilepsy

Johanna Elms, Kim L. Powell, Leena van Raay, Stefanie Dedeurwaerdere, Terence J. O'Brien, Margaret J. Morris

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Abstract

The mechanisms by which valproate, one of the most widely prescribed anti-epileptic drugs, suppresses seizures have not been fully elucidated but may involve up-regulation of neuropeptide Y (NPY). We investigated the effects of valproate treatment in Genetic Absence Epilepsy Rats from Strasbourg (GAERS) on brain NPY mRNA expression and seizure control. GAERS were administered either valproate (42 mg.kg-1 hr-1) or saline continuously for 5 days. Electroencephalograms were recorded for 24 hrs on treatment days 1, 3 and 5 and the percentage of time spent in seizure activity was analysed. NPY mRNA expression was measured in different brain regions using qPCR. Valproate treatment suppressed seizures by 80% in GAERS (p<0.05) and increased NPY mRNA expression in the thalamus (p<0.05) compared to saline treatment. These results demonstrate that long-term valproate treatment results in an upregulation of thalamic expression of NPY implicating this as a potential contributor to the mechanism by which valproate suppresses absence seizures.

Original languageEnglish
Article numbere73505
JournalPLoS ONE
Volume8
Issue number9
DOIs
Publication statusPublished - 9 Sep 2013
Externally publishedYes

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