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

Research output: Contribution to journalArticle

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.

Details

Authors
  • David P D Woldbye
  • Avtandil Nanobashvili
  • Andreas Toft Sörensen
  • Henriette Husum
  • Tom G Bolwig
  • Gunnar Sørensen
  • Patrik Ernfors
  • Merab Kokaia
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences

Keywords

  • kainate, epilepsy, zero magnesium, NPY, knockout mice, hippocampal kindling, brain slice
Original languageEnglish
Pages (from-to)760-772
JournalNeurobiology of Disease
Volume20
Issue number3
Publication statusPublished - 2005
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

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)

Related research output

Toft Sörensen, A., 2008, Institutionen för kliniska vetenskaper, Lunds universitet. 134 p.

Research output: ThesisDoctoral Thesis (compilation)

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