Long-term valproate treatment increases brain neuropeptide Y expression and decreases seizure expression in a genetic rat model of absence epilepsy

PLoS One. 2013 Sep 9;8(9):e73505. doi: 10.1371/journal.pone.0073505. eCollection 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / therapeutic use*
  • Brain / drug effects
  • Brain / metabolism
  • Epilepsy, Absence / drug therapy*
  • Epilepsy, Absence / genetics
  • Male
  • Neuropeptide Y / genetics*
  • Rats
  • Rats, Wistar
  • Seizures / drug therapy
  • Seizures / genetics
  • Up-Regulation / drug effects*
  • Valproic Acid / therapeutic use*

Substances

  • Anticonvulsants
  • Neuropeptide Y
  • Valproic Acid

Grants and funding

This work was funded by project grant support from the National Health and Medical Research Council (NHMRC grant #568729) of Australia to MJM and TJO. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript” to the Financial Disclosure.