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VEGF receptor-2 (flk-1) overexpression in mice counteracts focal epileptic seizures.

Nikitidou, Litsa LU ; Kanter Schlifke, Irene; Dhondt, Joke; Carmeliet, Peter; Lambrechts, Diether and Kokaia, Merab LU (2012) In PLoS ONE 7(7).
Abstract
Vascular endothelial growth factor (VEGF) was first described as an angiogenic agent, but has recently also been shown to exert various neurotrophic and neuroprotective effects in the nervous system. These effects of VEGF are mainly mediated by its receptor, VEGFR-2, which is also referred to as the fetal liver kinase receptor 1 (Flk-1). VEGF is up-regulated in neurons and glial cells after epileptic seizures and counteracts seizure-induced neurodegeneration. In vitro, VEGF administration suppresses ictal and interictal epileptiform activity caused by AP4 and 0 Mg(2+) via Flk-1 receptor. We therefore explored whether increased VEGF signaling through Flk-1 overexpression may regulate epileptogenesis and ictogenesis in vivo. To this extent,... (More)
Vascular endothelial growth factor (VEGF) was first described as an angiogenic agent, but has recently also been shown to exert various neurotrophic and neuroprotective effects in the nervous system. These effects of VEGF are mainly mediated by its receptor, VEGFR-2, which is also referred to as the fetal liver kinase receptor 1 (Flk-1). VEGF is up-regulated in neurons and glial cells after epileptic seizures and counteracts seizure-induced neurodegeneration. In vitro, VEGF administration suppresses ictal and interictal epileptiform activity caused by AP4 and 0 Mg(2+) via Flk-1 receptor. We therefore explored whether increased VEGF signaling through Flk-1 overexpression may regulate epileptogenesis and ictogenesis in vivo. To this extent, we used transgenic mice overexpressing Flk-1 postnatally in neurons. Intriguingly, Flk-1 overexpressing mice were characterized by an elevated threshold for seizure induction and a decreased duration of focal afterdischarges, indicating anti-ictal action. On the other hand, the kindling progression in these mice was similar to wild-type controls. No significant effects on blood vessels or glia cells, as assessed by Glut1 and GFAP immunohistochemistry, were detected. These results suggest that increased VEGF signaling via overexpression of Flk-1 receptors may directly affect seizure activity even without altering angiogenesis. Thus, Flk-1 could be considered as a novel target for developing future gene therapy strategies against ictal epileptic activity. (Less)
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organization
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publication status
published
subject
in
PLoS ONE
volume
7
issue
7
publisher
Public Library of Science
external identifiers
  • wos:000306366400032
  • pmid:22808185
  • scopus:84863769685
ISSN
1932-6203
DOI
10.1371/journal.pone.0040535
language
English
LU publication?
yes
id
3d403fd6-1aca-44dc-af43-83a2236888ff (old id 2966986)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22808185?dopt=Abstract
date added to LUP
2012-08-09 19:49:47
date last changed
2017-03-03 14:32:55
@article{3d403fd6-1aca-44dc-af43-83a2236888ff,
  abstract     = {Vascular endothelial growth factor (VEGF) was first described as an angiogenic agent, but has recently also been shown to exert various neurotrophic and neuroprotective effects in the nervous system. These effects of VEGF are mainly mediated by its receptor, VEGFR-2, which is also referred to as the fetal liver kinase receptor 1 (Flk-1). VEGF is up-regulated in neurons and glial cells after epileptic seizures and counteracts seizure-induced neurodegeneration. In vitro, VEGF administration suppresses ictal and interictal epileptiform activity caused by AP4 and 0 Mg(2+) via Flk-1 receptor. We therefore explored whether increased VEGF signaling through Flk-1 overexpression may regulate epileptogenesis and ictogenesis in vivo. To this extent, we used transgenic mice overexpressing Flk-1 postnatally in neurons. Intriguingly, Flk-1 overexpressing mice were characterized by an elevated threshold for seizure induction and a decreased duration of focal afterdischarges, indicating anti-ictal action. On the other hand, the kindling progression in these mice was similar to wild-type controls. No significant effects on blood vessels or glia cells, as assessed by Glut1 and GFAP immunohistochemistry, were detected. These results suggest that increased VEGF signaling via overexpression of Flk-1 receptors may directly affect seizure activity even without altering angiogenesis. Thus, Flk-1 could be considered as a novel target for developing future gene therapy strategies against ictal epileptic activity.},
  articleno    = {e40535},
  author       = {Nikitidou, Litsa and Kanter Schlifke, Irene and Dhondt, Joke and Carmeliet, Peter and Lambrechts, Diether and Kokaia, Merab},
  issn         = {1932-6203},
  language     = {eng},
  number       = {7},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {VEGF receptor-2 (flk-1) overexpression in mice counteracts focal epileptic seizures.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0040535},
  volume       = {7},
  year         = {2012},
}