Combined gene overexpression of neuropeptide Y and its receptor Y5 in the hippocampus suppresses seizures.

Casper René Gøtzsche; Litsa Nikitidou; Andreas Toft Sørensen; Mikkel V Olesen; Gunnar Sørensen; Søren Hofman Oliveira Christiansen; Mikael Ängehagen; David Paul Drucker Woldbye; Merab Kokaia

doi:10.1016/j.nbd.2011.08.012

Combined gene overexpression of neuropeptide Y and its receptor Y5 in the hippocampus suppresses seizures.

Casper René Gøtzsche, Litsa Nikitidou, Andreas Toft Sørensen, Mikkel V Olesen, Gunnar Sørensen, Søren Hofman Oliveira Christiansen, Mikael Ängehagen, David Paul Drucker Woldbye, Merab Kokaia

35 Citations (Scopus)

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.

Original language	English
Journal	Neurobiology of Disease
Volume	45
Pages (from-to)	288-96
Number of pages	9
ISSN	0969-9961
DOIs	https://doi.org/10.1016/j.nbd.2011.08.012
Publication status	Published - Jan 2012

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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.",

author = "G{\o}tzsche, {Casper Ren{\'e}} and Litsa Nikitidou and S{\o}rensen, {Andreas Toft} and Olesen, {Mikkel V} and Gunnar S{\o}rensen and Christiansen, {S{\o}ren Hofman Oliveira} and Mikael {\"A}ngehagen and Woldbye, {David Paul Drucker} and Merab Kokaia",

year = "2012",

month = jan,

doi = "10.1016/j.nbd.2011.08.012",

language = "English",

volume = "45",

pages = "288--96",

journal = "Neurobiology of Disease",

issn = "0969-9961",

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T1 - Combined gene overexpression of neuropeptide Y and its receptor Y5 in the hippocampus suppresses seizures.

AU - Gøtzsche, Casper René

AU - Nikitidou, Litsa

AU - Sørensen, Andreas Toft

AU - Olesen, Mikkel V

AU - Sørensen, Gunnar

AU - Christiansen, Søren Hofman Oliveira

AU - Ängehagen, Mikael

AU - Woldbye, David Paul Drucker

AU - Kokaia, Merab

PY - 2012/1

Y1 - 2012/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.nbd.2011.08.012

DO - 10.1016/j.nbd.2011.08.012

M3 - Journal article

C2 - 21884793

SN - 0969-9961

VL - 45

SP - 288

EP - 296

JO - Neurobiology of Disease

JF - Neurobiology of Disease

ER -

Combined gene overexpression of neuropeptide Y and its receptor Y5 in the hippocampus suppresses seizures.

Abstract

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