Adeno-associated viral vector-induced overexpression of neuropeptide Y Y2 receptors in the hippocampus suppresses seizures.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Gene therapy using recombinant adeno-associated viral vectors overexpressing neuropeptide Y in the hippocampus exerts seizure-suppressant effects in rodent epilepsy models and is currently considered for clinical application in patients with intractable mesial temporal lobe epilepsy. Seizure suppression by neuropeptide Y in the hippocampus is predominantly mediated by Y2 receptors, which, together with neuropeptide Y, are upregulated after seizures as a compensatory mechanism. To explore whether such upregulation could prevent seizures, we overexpressed Y2 receptors in the hippocampus using recombinant adeno-associated viral vectors. In two temporal lobe epilepsy models, electrical kindling and kainate-induced seizures, vector-based transduction of Y2 receptor complementary DNA in the hippocampus of adult rats exerted seizure-suppressant effects. Simultaneous overexpression of Y2 and neuropeptide Y had a more pronounced seizure-suppressant effect. These results demonstrate that overexpression of Y2 receptors (alone or in combination with neuropeptide Y) could be an alternative strategy for epilepsy treatment.

Detaljer

Författare
  • David P D Woldbye
  • Mikael Ängehagen
  • Casper R Gøtzsche
  • Heidi Elbrønd-Bek
  • Andreas Toft Sörensen
  • Søren H Christiansen
  • Mikkel V Olesen
  • Litsa Nikitidou
  • Thomas V O Hansen
  • Irene Kanter Schlifke
  • Merab Kokaia
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurologi
Originalspråkengelska
Sidor (från-till)2778-2788
TidskriftBrain
Volym133
Utgåva nummerPt 9
StatusPublished - 2010
PublikationskategoriForskning
Peer review utfördJa