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Development and persistence of kindling epilepsy are impaired in mice lacking glial cell line-derived neurotrophic factor family receptor α2

Nanobashvili, Avtandil LU ; Airaksinen, Matti S. ; Kokaia, Merab LU ; Rossi, Jari ; Asztély, Fredrik LU ; Olofsdotter, Klara LU ; Mohapel, Paul LU ; Saarma, Mart ; Lindvall, Olle LU and Kokaia, Zaal LU (2000) In Proceedings of the National Academy of Sciences of the United States of America 97(22). p.12312-12317
Abstract

Seizure activity regulates gene expression for glial cell line-derived neurotrophic factor (GDNF) and neurturin (NRTN), and their receptor components, the transmembrane c-Ret tyrosine kinase and the glycosylphosphatidylinositol-anchored GDNF family receptor (GFR) α1 and α2 in limbic structures. We demonstrate here that epileptogenesis, as assessed in the hippocampal kindling model, is markedly suppressed in mice lacking GFRα2. Moreover, at 6 to 8 wk after having reached the epileptic state, the hyperexcitability is lower in GFRα2 knock-out mice as compared with wild-type mice. These results provide evidence that signaling through GFRα2 is involved in mechanisms regulating the development and persistence of kindling epilepsy. Our data... (More)

Seizure activity regulates gene expression for glial cell line-derived neurotrophic factor (GDNF) and neurturin (NRTN), and their receptor components, the transmembrane c-Ret tyrosine kinase and the glycosylphosphatidylinositol-anchored GDNF family receptor (GFR) α1 and α2 in limbic structures. We demonstrate here that epileptogenesis, as assessed in the hippocampal kindling model, is markedly suppressed in mice lacking GFRα2. Moreover, at 6 to 8 wk after having reached the epileptic state, the hyperexcitability is lower in GFRα2 knock-out mice as compared with wild-type mice. These results provide evidence that signaling through GFRα2 is involved in mechanisms regulating the development and persistence of kindling epilepsy. Our data suggest that GDNF and NRTN may modulate seizure susceptibility by altering the function of hilar neuropeptide Y-containing interneurons and entorhinal cortical afferents at dentate granule cell synapses.

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author
publishing date
type
Contribution to journal
publication status
published
subject
in
Proceedings of the National Academy of Sciences of the United States of America
volume
97
issue
22
pages
6 pages
publisher
National Acad Sciences
external identifiers
  • pmid:11050250
  • scopus:12944293011
ISSN
0027-8424
DOI
10.1073/pnas.97.22.12312
language
English
LU publication?
no
id
82ce4316-3aa5-41df-ae3d-5db505071129
date added to LUP
2019-09-03 17:00:11
date last changed
2020-01-13 02:19:36
@article{82ce4316-3aa5-41df-ae3d-5db505071129,
  abstract     = {<p>Seizure activity regulates gene expression for glial cell line-derived neurotrophic factor (GDNF) and neurturin (NRTN), and their receptor components, the transmembrane c-Ret tyrosine kinase and the glycosylphosphatidylinositol-anchored GDNF family receptor (GFR) α1 and α2 in limbic structures. We demonstrate here that epileptogenesis, as assessed in the hippocampal kindling model, is markedly suppressed in mice lacking GFRα2. Moreover, at 6 to 8 wk after having reached the epileptic state, the hyperexcitability is lower in GFRα2 knock-out mice as compared with wild-type mice. These results provide evidence that signaling through GFRα2 is involved in mechanisms regulating the development and persistence of kindling epilepsy. Our data suggest that GDNF and NRTN may modulate seizure susceptibility by altering the function of hilar neuropeptide Y-containing interneurons and entorhinal cortical afferents at dentate granule cell synapses.</p>},
  author       = {Nanobashvili, Avtandil and Airaksinen, Matti S. and Kokaia, Merab and Rossi, Jari and Asztély, Fredrik and Olofsdotter, Klara and Mohapel, Paul and Saarma, Mart and Lindvall, Olle and Kokaia, Zaal},
  issn         = {0027-8424},
  language     = {eng},
  month        = {10},
  number       = {22},
  pages        = {12312--12317},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences of the United States of America},
  title        = {Development and persistence of kindling epilepsy are impaired in mice lacking glial cell line-derived neurotrophic factor family receptor α2},
  url          = {http://dx.doi.org/10.1073/pnas.97.22.12312},
  doi          = {10.1073/pnas.97.22.12312},
  volume       = {97},
  year         = {2000},
}