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Author Notes:

Address correspondence to Ray Dingledine, Department of Pharmacology, Emory University, Atlanta, GA 30322, U.S.A. rdingledine@pharm.emory.edu.

UCB, which sells levetiracetam, sponsored BH to attend the 2006 annual meeting of the American Epilepsy Society.

LG received from UCB a travel grant and honorarium to chair a satellite meeting.

The other authors have no potential conflicts of interest to disclose.

We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Subjects:

Research Funding:

This study was supported by The Norwegian Chapter of The International League Against Epilepsy; The Department of Neurology, Division of Clinical Neuroscience, Rikshospitalet Medical Centre; and NINDS (RD).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Clinical Neurology
  • Neurosciences & Neurology
  • Epilepsy
  • mRNA
  • Transcription
  • Antiepileptic drugs
  • Brain region
  • ANTIEPILEPTIC DRUG LEVETIRACETAM
  • SODIUM-CHANNELS
  • P-GLYCOPROTEIN
  • BINDING-SITE
  • GABA
  • EPILEPSY
  • INHIBITION
  • VALPROATE
  • MECHANISM
  • RECEPTOR

Region-specific changes in gene expression in rat brain after chronic treatment with levetiracetam or phenytoin

Tools:

Journal Title:

Epilepsia

Volume:

Volume 51, Number 9

Publisher:

, Pages 1714-1720

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Purpose: It is commonly assumed that antiepileptic drugs (AEDs) act similarly in the various parts of the brain as long as their molecular targets are present. A few experimental studies on metabolic effects of vigabatrin, levetiracetam, valproate, and lamotrigine have shown that these drugs may act differently in different brain regions. We examined effects of chronic treatment with levetiracetam or phenytoin on mRNA levels to detect regional drug effects in a broad, nonbiased manner. Methods: mRNA levels were monitored in three brain regions with oligonucleotide-based microarrays. Results: Levetiracetam (150 mg/kg for 90 days) changed the expression of 65 genes in pons/medulla oblongata, two in hippocampus, and one in frontal cortex. Phenytoin (75 mg/kg), in contrast, changed the expression of only three genes in pons/medulla oblongata, but 64 genes in hippocampus, and 327 genes in frontal cortex. Very little overlap between regions or drug treatments was observed with respect to effects on gene expression. Discussion: We conclude that chronic treatment with levetiracetam or phenytoin causes region-specific and highly differential effects on gene expression in the brain. Regional effects on gene expression could reflect regional differences in molecular targets of AEDs, and they could influence the clinical profiles of AEDs.

Copyright information:

© 2010 International League Against Epilepsy.

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