Adeno-associated viral vector-induced overexpression of neuropeptide Y Y2 receptors in the hippocampus suppresses seizures

David Paul Drucker Woldbye; Mikael Ängehagen; Casper René Gøtzsche; Heidi Elbrønd-Bek; Andreas Toft Sørensen; Søren Hofman Oliveira Christiansen; Mikkel V. Olesen; Litsa Nikitidou; Thomas v. O. Hansen; Irene Kanter-Schlifke; Merab Kokaia

doi:10.1093/brain/awq219

Adeno-associated viral vector-induced overexpression of neuropeptide Y Y2 receptors in the hippocampus suppresses seizures

David Paul Drucker Woldbye, Mikael Ängehagen, Casper René Gøtzsche, Heidi Elbrønd-Bek, Andreas Toft Sørensen, Søren Hofman Oliveira Christiansen, Mikkel V. Olesen, Litsa Nikitidou, Thomas v. O. Hansen, Irene Kanter-Schlifke, Merab Kokaia

64 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Brain
Volume	133
Issue number	9
Pages (from-to)	2778-88
Number of pages	10
ISSN	0006-8950
DOIs	https://doi.org/10.1093/brain/awq219
Publication status	Published - Sept 2010

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Woldbye, D. P. D., Ängehagen, M., Gøtzsche, C. R., Elbrønd-Bek, H., Sørensen, A. T., Christiansen, S. H. O., Olesen, M. V., Nikitidou, L., Hansen, T. V. O., Kanter-Schlifke, I., & Kokaia, M. (2010). Adeno-associated viral vector-induced overexpression of neuropeptide Y Y2 receptors in the hippocampus suppresses seizures. Brain, 133(9), 2778-88. https://doi.org/10.1093/brain/awq219

Woldbye, DPD, Ängehagen, M, Gøtzsche, CR, Elbrønd-Bek, H, Sørensen, AT, Christiansen, SHO, Olesen, MV, Nikitidou, L, Hansen, TVO, Kanter-Schlifke, I & Kokaia, M 2010, 'Adeno-associated viral vector-induced overexpression of neuropeptide Y Y2 receptors in the hippocampus suppresses seizures', Brain, vol. 133, no. 9, pp. 2778-88. https://doi.org/10.1093/brain/awq219

@article{ddcaf2ef54b043e5a8d96b9ce6c159c4,

title = "Adeno-associated viral vector-induced overexpression of neuropeptide Y Y2 receptors in the hippocampus suppresses seizures",

abstract = "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.",

author = "Woldbye, {David Paul Drucker} and Mikael {\"A}ngehagen and G{\o}tzsche, {Casper Ren{\'e}} and Heidi Elbr{\o}nd-Bek and S{\o}rensen, {Andreas Toft} and Christiansen, {S{\o}ren Hofman Oliveira} and Olesen, {Mikkel V.} and Litsa Nikitidou and Hansen, {Thomas v. O.} and Irene Kanter-Schlifke and Merab Kokaia",

year = "2010",

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doi = "10.1093/brain/awq219",

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T1 - Adeno-associated viral vector-induced overexpression of neuropeptide Y Y2 receptors in the hippocampus suppresses seizures

AU - Woldbye, David Paul Drucker

AU - Ängehagen, Mikael

AU - Gøtzsche, Casper René

AU - Elbrønd-Bek, Heidi

AU - Sørensen, Andreas Toft

AU - Christiansen, Søren Hofman Oliveira

AU - Olesen, Mikkel V.

AU - Nikitidou, Litsa

AU - Hansen, Thomas v. O.

AU - Kanter-Schlifke, Irene

AU - Kokaia, Merab

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N2 - 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.

AB - 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.

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DO - 10.1093/brain/awq219

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SN - 0006-8950

VL - 133

SP - 2778

EP - 2788

JO - Brain

JF - Brain

IS - 9

ER -

Adeno-associated viral vector-induced overexpression of neuropeptide Y Y2 receptors in the hippocampus suppresses seizures

Abstract

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