Combined gene overexpression of neuropeptide Y and its receptor Y5 in the hippocampus suppresses seizures
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...
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Elsevier
2012-01-01
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Series: | Neurobiology of Disease |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996111002786 |
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author | Casper R. Gøtzsche Litsa Nikitidou Andreas T. Sørensen Mikkel V. Olesen Gunnar Sørensen Søren H.O. Christiansen Mikael Ängehagen David P.D. Woldbye Merab Kokaia |
author_facet | Casper R. Gøtzsche Litsa Nikitidou Andreas T. Sørensen Mikkel V. Olesen Gunnar Sørensen Søren H.O. Christiansen Mikael Ängehagen David P.D. Woldbye Merab Kokaia |
author_sort | Casper R. Gøtzsche |
collection | DOAJ |
description | 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. |
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publishDate | 2012-01-01 |
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spelling | doaj.art-12d3c1ac474e4b0291fb9c0f97bdce612022-12-21T21:55:46ZengElsevierNeurobiology of Disease1095-953X2012-01-01451288296Combined gene overexpression of neuropeptide Y and its receptor Y5 in the hippocampus suppresses seizuresCasper R. Gøtzsche0Litsa Nikitidou1Andreas T. Sørensen2Mikkel V. Olesen3Gunnar Sørensen4Søren H.O. Christiansen5Mikael Ängehagen6David P.D. Woldbye7Merab Kokaia8Protein Laboratory, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark; Laboratory of Neuropsychiatry, Psychiatric Centre Copenhagen & Department of Neuroscience and Pharmacology, University of Copenhagen, DenmarkExperimental Epilepsy Group, Wallenberg Neuroscience Center, Lund University Hospital, SwedenExperimental Epilepsy Group, Wallenberg Neuroscience Center, Lund University Hospital, SwedenLaboratory of Neuropsychiatry, Psychiatric Centre Copenhagen & Department of Neuroscience and Pharmacology, University of Copenhagen, DenmarkLaboratory of Neuropsychiatry, Psychiatric Centre Copenhagen & Department of Neuroscience and Pharmacology, University of Copenhagen, DenmarkProtein Laboratory, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark; Laboratory of Neuropsychiatry, Psychiatric Centre Copenhagen & Department of Neuroscience and Pharmacology, University of Copenhagen, DenmarkExperimental Epilepsy Group, Wallenberg Neuroscience Center, Lund University Hospital, SwedenProtein Laboratory, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark; Laboratory of Neuropsychiatry, Psychiatric Centre Copenhagen & Department of Neuroscience and Pharmacology, University of Copenhagen, DenmarkExperimental Epilepsy Group, Wallenberg Neuroscience Center, Lund University Hospital, Sweden; Corresponding author at: Experimental Epilepsy Group, Wallenberg Neuroscience Center, BMC A-11, Lund University Hospital, Lund, Sweden. Fax: +46 462 220 560.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.http://www.sciencedirect.com/science/article/pii/S0969996111002786Y5 neuropeptide Y receptorAdeno-associated viral vectorsKainic acid seizuresGene therapy |
spellingShingle | Casper R. Gøtzsche Litsa Nikitidou Andreas T. Sørensen Mikkel V. Olesen Gunnar Sørensen Søren H.O. Christiansen Mikael Ängehagen David P.D. Woldbye Merab Kokaia Combined gene overexpression of neuropeptide Y and its receptor Y5 in the hippocampus suppresses seizures Neurobiology of Disease Y5 neuropeptide Y receptor Adeno-associated viral vectors Kainic acid seizures Gene therapy |
title | Combined gene overexpression of neuropeptide Y and its receptor Y5 in the hippocampus suppresses seizures |
title_full | Combined gene overexpression of neuropeptide Y and its receptor Y5 in the hippocampus suppresses seizures |
title_fullStr | Combined gene overexpression of neuropeptide Y and its receptor Y5 in the hippocampus suppresses seizures |
title_full_unstemmed | Combined gene overexpression of neuropeptide Y and its receptor Y5 in the hippocampus suppresses seizures |
title_short | Combined gene overexpression of neuropeptide Y and its receptor Y5 in the hippocampus suppresses seizures |
title_sort | combined gene overexpression of neuropeptide y and its receptor y5 in the hippocampus suppresses seizures |
topic | Y5 neuropeptide Y receptor Adeno-associated viral vectors Kainic acid seizures Gene therapy |
url | http://www.sciencedirect.com/science/article/pii/S0969996111002786 |
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