title: Combined gene overexpression of neuropeptide Y and its receptor Y5 in the hippocampus suppresses seizures.
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.
authors: Protein Laboratory, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark.
authors: Casper R
authors: CR
authors: Gøtzsche
authors: Litsa
authors: L
authors: Nikitidou
authors: Andreas T
authors: AT
authors: Sørensen
authors: Mikkel V
authors: MV
authors: Olesen
authors: Gunnar
authors: G
authors: Sørensen
authors: Søren H O
authors: SH
authors: Christiansen
authors: Mikael
authors: M
authors: Ängehagen
authors: David P D
authors: DP
authors: Woldbye
authors: Merab
authors: M
authors: Kokaia
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000378:metabolism*; D007608:Kainic Acid; D007696:Kindling, Neurologic / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000235:genetics* / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism
chemical_list: D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor; D007608:Kainic Acid