Adeno-associated Viral Vector-Induced Overexpression of Neuropeptide Y Y2 Receptors in the Hippocampus Suppresses Seizures

Brain. 2010 Sep;133(9):2778-88. doi: 10.1093/brain/awq219. Epub 2010 Aug 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Disease Models, Animal
  • Electric Stimulation / adverse effects
  • Genetic Therapy / methods*
  • Genetic Vectors / physiology
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacokinetics
  • Hippocampus / metabolism*
  • Kainic Acid / adverse effects
  • Kindling, Neurologic / genetics
  • Kindling, Neurologic / physiology
  • Male
  • Protein Binding / genetics
  • Radiography / methods
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Receptors, Neuropeptide Y / genetics
  • Receptors, Neuropeptide Y / metabolism
  • Receptors, Neuropeptide Y / therapeutic use*
  • Seizures / etiology
  • Seizures / pathology*
  • Seizures / therapy*
  • Sulfur Isotopes / pharmacokinetics
  • Transcription, Genetic / physiology

Substances

  • Receptors, Neuropeptide Y
  • Sulfur Isotopes
  • neuropeptide Y2 receptor
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Kainic Acid