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Differential suppression of seizures via Y2 and Y5 neuropeptide Y receptors.

Woldbye, David P D ; Nanobashvili, Avtandil LU ; Toft Sörensen, Andreas LU ; Husum, Henriette ; Bolwig, Tom G ; Sørensen, Gunnar ; Ernfors, Patrik and Kokaia, Merab LU (2005) In Neurobiology of Disease 20(3). p.760-772
Abstract
Neuropepticle Y (NPY) prominently inhibits epileptic seizures in different animal models. The NPY receptors mediating this effect remain controversial partially due to lack of highly selective agonists and antagonists. To circumvent this problem, we used various NPY receptor knockout mice with the same genetic background and explored anti-epileptic action of NPY in vitro and in vivo. In Y2 (Y2-/-) and Y5 (Y5-/-) receptor knockouts, NPY partially inhibited 0 Mg2(+)-induced epileptiform activity in hippocampal slices. In contrast, in double knockouts (Y2Y5-/-), NPY had no effect, suggesting that in the hippocampus in vitro both receptors mediate anti-epileptiform action of NPY in an additive manner. Systemic kainate induced more severe... (More)
Neuropepticle Y (NPY) prominently inhibits epileptic seizures in different animal models. The NPY receptors mediating this effect remain controversial partially due to lack of highly selective agonists and antagonists. To circumvent this problem, we used various NPY receptor knockout mice with the same genetic background and explored anti-epileptic action of NPY in vitro and in vivo. In Y2 (Y2-/-) and Y5 (Y5-/-) receptor knockouts, NPY partially inhibited 0 Mg2(+)-induced epileptiform activity in hippocampal slices. In contrast, in double knockouts (Y2Y5-/-), NPY had no effect, suggesting that in the hippocampus in vitro both receptors mediate anti-epileptiform action of NPY in an additive manner. Systemic kainate induced more severe seizures in Y5-/- and Y2Y5-/-, but not in Y2-/- mice, as compared to wild-type mice. Moreover, kainate seizures were aggravated by administration of the Y5 antagonist L-152,804 in wild-type mice. In Y5-/- mice, hippocampal kindling progressed faster, and afterdischarge durations were longer in amygdala, but not in hippocampus, as compared to wild-type controls. Taken together, these data suggest that, in mice, both Y2 and Y5 receptors regulate hippocampa seizures in vitro, while activation of Y5 receptors in extra-hippocampa: regions reduces generalized seizures in vivo. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
kainate, epilepsy, zero magnesium, NPY, knockout mice, hippocampal kindling, brain slice
in
Neurobiology of Disease
volume
20
issue
3
pages
760 - 772
publisher
Elsevier
external identifiers
  • wos:000233739100015
  • pmid:15979311
  • scopus:27744560977
ISSN
0969-9961
DOI
10.1016/j.nbd.2005.05.010
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neurology, Lund (013027000), Restorative Neurology (0131000160)
id
20cf1378-79d0-413d-be30-e02dbc2c9341 (old id 139736)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15979311&query_hl=85
http://www.sciencedirect.com/science/article/pii/S0969996105001476
date added to LUP
2016-04-01 12:13:49
date last changed
2022-02-11 03:48:35
@article{20cf1378-79d0-413d-be30-e02dbc2c9341,
  abstract     = {{Neuropepticle Y (NPY) prominently inhibits epileptic seizures in different animal models. The NPY receptors mediating this effect remain controversial partially due to lack of highly selective agonists and antagonists. To circumvent this problem, we used various NPY receptor knockout mice with the same genetic background and explored anti-epileptic action of NPY in vitro and in vivo. In Y2 (Y2-/-) and Y5 (Y5-/-) receptor knockouts, NPY partially inhibited 0 Mg2(+)-induced epileptiform activity in hippocampal slices. In contrast, in double knockouts (Y2Y5-/-), NPY had no effect, suggesting that in the hippocampus in vitro both receptors mediate anti-epileptiform action of NPY in an additive manner. Systemic kainate induced more severe seizures in Y5-/- and Y2Y5-/-, but not in Y2-/- mice, as compared to wild-type mice. Moreover, kainate seizures were aggravated by administration of the Y5 antagonist L-152,804 in wild-type mice. In Y5-/- mice, hippocampal kindling progressed faster, and afterdischarge durations were longer in amygdala, but not in hippocampus, as compared to wild-type controls. Taken together, these data suggest that, in mice, both Y2 and Y5 receptors regulate hippocampa seizures in vitro, while activation of Y5 receptors in extra-hippocampa: regions reduces generalized seizures in vivo.}},
  author       = {{Woldbye, David P D and Nanobashvili, Avtandil and Toft Sörensen, Andreas and Husum, Henriette and Bolwig, Tom G and Sørensen, Gunnar and Ernfors, Patrik and Kokaia, Merab}},
  issn         = {{0969-9961}},
  keywords     = {{kainate; epilepsy; zero magnesium; NPY; knockout mice; hippocampal kindling; brain slice}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{760--772}},
  publisher    = {{Elsevier}},
  series       = {{Neurobiology of Disease}},
  title        = {{Differential suppression of seizures via Y2 and Y5 neuropeptide Y receptors.}},
  url          = {{http://dx.doi.org/10.1016/j.nbd.2005.05.010}},
  doi          = {{10.1016/j.nbd.2005.05.010}},
  volume       = {{20}},
  year         = {{2005}},
}