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

Woldbye, David P D ; Ängehagen, Mikael LU ; Gøtzsche, Casper R ; Elbrønd-Bek, Heidi ; Toft Sörensen, Andreas LU ; Christiansen, Søren H ; Olesen, Mikkel V ; Nikitidou, Litsa LU ; Hansen, Thomas V O and Kanter Schlifke, Irene LU , et al. (2010) In Brain 133(Pt 9). p.2778-2788
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Brain
volume
133
issue
Pt 9
pages
2778 - 2788
publisher
Oxford University Press
external identifiers
  • wos:000281529000027
  • pmid:20688813
  • scopus:77956385206
  • pmid:20688813
ISSN
1460-2156
DOI
10.1093/brain/awq219
language
English
LU publication?
yes
id
39507676-89d0-4e1a-838a-70d8c7ed15c0 (old id 1665527)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20688813?dopt=Abstract
date added to LUP
2016-04-04 07:40:25
date last changed
2022-04-15 19:20:23
@article{39507676-89d0-4e1a-838a-70d8c7ed15c0,
  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 P D and Ängehagen, Mikael and Gøtzsche, Casper R and Elbrønd-Bek, Heidi and Toft Sörensen, Andreas and Christiansen, Søren H and Olesen, Mikkel V and Nikitidou, Litsa and Hansen, Thomas V O and Kanter Schlifke, Irene and Kokaia, Merab}},
  issn         = {{1460-2156}},
  language     = {{eng}},
  number       = {{Pt 9}},
  pages        = {{2778--2788}},
  publisher    = {{Oxford University Press}},
  series       = {{Brain}},
  title        = {{Adeno-associated viral vector-induced overexpression of neuropeptide Y Y2 receptors in the hippocampus suppresses seizures.}},
  url          = {{http://dx.doi.org/10.1093/brain/awq219}},
  doi          = {{10.1093/brain/awq219}},
  volume       = {{133}},
  year         = {{2010}},
}