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...

Full description

Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2012-01-01
Series:Neurobiology of Disease
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996111002786
_version_ 1818677488611491840
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.
first_indexed 2024-12-17T09:00:10Z
format Article
id doaj.art-12d3c1ac474e4b0291fb9c0f97bdce61
institution Directory Open Access Journal
issn 1095-953X
language English
last_indexed 2024-12-17T09:00:10Z
publishDate 2012-01-01
publisher Elsevier
record_format Article
series Neurobiology of Disease
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
work_keys_str_mv AT casperrgøtzsche combinedgeneoverexpressionofneuropeptideyanditsreceptory5inthehippocampussuppressesseizures
AT litsanikitidou combinedgeneoverexpressionofneuropeptideyanditsreceptory5inthehippocampussuppressesseizures
AT andreastsørensen combinedgeneoverexpressionofneuropeptideyanditsreceptory5inthehippocampussuppressesseizures
AT mikkelvolesen combinedgeneoverexpressionofneuropeptideyanditsreceptory5inthehippocampussuppressesseizures
AT gunnarsørensen combinedgeneoverexpressionofneuropeptideyanditsreceptory5inthehippocampussuppressesseizures
AT sørenhochristiansen combinedgeneoverexpressionofneuropeptideyanditsreceptory5inthehippocampussuppressesseizures
AT mikaelangehagen combinedgeneoverexpressionofneuropeptideyanditsreceptory5inthehippocampussuppressesseizures
AT davidpdwoldbye combinedgeneoverexpressionofneuropeptideyanditsreceptory5inthehippocampussuppressesseizures
AT merabkokaia combinedgeneoverexpressionofneuropeptideyanditsreceptory5inthehippocampussuppressesseizures