Combined gene overexpression of neuropeptide Y and its receptor Y5 in the hippocampus suppresses seizures

Research output: Contribution to journalArticle

Abstract

We recently demonstrated that recombinant adeno-associated viral vector-induced hippocampal overexpression of neuropeptide Y receptor, Y2, exerts a seizure-suppressant effect in kindling and kainate-induced models of epilepsy in rats. Interestingly, additional overexpression of neuropeptide Y in the hippocampus strengthened the seizure-suppressant effect of transgene Y2 receptors. Here we show for the first time that another neuropeptide Y receptor, Y5, can also be overexpressed in the hippocampus. However, unlike Y2 receptor overexpression, transgene Y5 receptors in the hippocampus had no effect on kainate-induced motor seizures in rats. However, combined overexpression of Y5 receptors and neuropeptide Y exerted prominent suppression of seizures. This seizure-suppressant effect of combination gene therapy with Y5 receptors and neuropeptide Y was significantly stronger as compared to neuropeptide Y overexpression alone. These results suggest that overexpression of Y5 receptors in combination with neuropeptide Y could be an alternative approach for more effective suppression of hippocampal seizures. (C) 2011 Elsevier Inc. All rights reserved.

Details

Authors
  • Casper R. Gotzsche
  • Litsa Nikitidou
  • Andreas Toft Sörensen
  • Mikkel V. Olesen
  • Gunnar Sorensen
  • Soren H. O. Christiansen
  • Mikael Ängehagen
  • David P. D. Woldbye
  • Merab Kokaia
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences

Keywords

  • Y5 neuropeptide Y receptor, Adeno-associated viral vectors, Kainic acid, seizures, Gene therapy
Original languageEnglish
Pages (from-to)288-296
JournalNeurobiology of Disease
Volume45
Issue number1
Publication statusPublished - 2012
Publication categoryResearch
Peer-reviewedYes

Related research output

Nikitidou, L., 2013, Neurology, Lund. 110 p.

Research output: ThesisDoctoral Thesis (compilation)

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