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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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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
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
2010-09-02 11:02:45
date last changed
2018-07-15 04:18:20
@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},
  volume       = {133},
  year         = {2010},
}