Authors:
David P. D. Woldbye, Mikael Ängehagen, Casper R. Gøtzsche, Heidi Elbrønd-Bek, Andreas T. Sørensen, Søren H. Christiansen, Mikkel V. Olesen, Litsa Nikitidou, Thomas v. O. Hansen, Irene Kanter-Schlifke, and Merab Kokaia
Summary:
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.
Source:
Brain; Vol. 133, Issue 9, 2778-2788 (08/05/10)