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Suppressed kindling epileptogenesis in mice with ectopic overexpression of galanin

Kokaia, Merab LU ; Holmberg, Kristina; Nanobashvili, Avtandil LU ; Xu, Zhi-Qing D.; Kokaia, Zaal LU ; Lendahl, Urban; Hilke, Susanne; Theodorsson, Elvar; Kahl, Ulrika and Bartfai, Tamas, et al. (2001) In Proceedings of the National Academy of Sciences 98(24). p.14006-14011
Abstract
The neuropeptide galanin has been shown to suppress epileptic seizures. In cortical and hippocampal areas, galanin is normally mainly expressed in noradrenergic afferents. We have generated a mouse overexpressing galanin in neurons under the platelet-derived growth factor B promoter. RIA and HPLC analysis revealed up to 8-fold higher levels of galanin in transgenic as compared with wild-type mice. Ectopic galanin overexpression was detected especially in dentate granule cells and hippocampal and cortical pyramidal neurons. Galanin-overexpressing mice showed retardation of seizure generalization during hippocampal kindling, a model for human complex partial epilepsy. The high levels of galanin in mossy fibers found in the transgenic mice... (More)
The neuropeptide galanin has been shown to suppress epileptic seizures. In cortical and hippocampal areas, galanin is normally mainly expressed in noradrenergic afferents. We have generated a mouse overexpressing galanin in neurons under the platelet-derived growth factor B promoter. RIA and HPLC analysis revealed up to 8-fold higher levels of galanin in transgenic as compared with wild-type mice. Ectopic galanin overexpression was detected especially in dentate granule cells and hippocampal and cortical pyramidal neurons. Galanin-overexpressing mice showed retardation of seizure generalization during hippocampal kindling, a model for human complex partial epilepsy. The high levels of galanin in mossy fibers found in the transgenic mice were further increased after seizures. Frequency facilitation of field excitatory postsynaptic potentials, a form of short-term synaptic plasticity assessed in hippocampal slices, was reduced in mossy fiber-CA3 cell synapses of galanin-overexpressing mice, indicating suppressed glutamate release. This effect was reversed by application of the putative galanin receptor antagonist M35. These data provide evidence that ectopically overexpressed galanin can be released and dampen the development of epilepsy by means of receptor-mediated action, at least partly by reducing glutamate release from mossy fibers. (Less)
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Proceedings of the National Academy of Sciences
volume
98
issue
24
pages
14006 - 14011
publisher
National Acad Sciences
external identifiers
  • pmid:11698649
  • scopus:0035923608
ISSN
1091-6490
DOI
10.1073/pnas.231496298
language
English
LU publication?
yes
id
78d71f76-076e-43e1-8b5e-a8162303ea3d (old id 1121974)
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2008-07-01 14:39:23
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2018-05-29 12:19:03
@article{78d71f76-076e-43e1-8b5e-a8162303ea3d,
  abstract     = {The neuropeptide galanin has been shown to suppress epileptic seizures. In cortical and hippocampal areas, galanin is normally mainly expressed in noradrenergic afferents. We have generated a mouse overexpressing galanin in neurons under the platelet-derived growth factor B promoter. RIA and HPLC analysis revealed up to 8-fold higher levels of galanin in transgenic as compared with wild-type mice. Ectopic galanin overexpression was detected especially in dentate granule cells and hippocampal and cortical pyramidal neurons. Galanin-overexpressing mice showed retardation of seizure generalization during hippocampal kindling, a model for human complex partial epilepsy. The high levels of galanin in mossy fibers found in the transgenic mice were further increased after seizures. Frequency facilitation of field excitatory postsynaptic potentials, a form of short-term synaptic plasticity assessed in hippocampal slices, was reduced in mossy fiber-CA3 cell synapses of galanin-overexpressing mice, indicating suppressed glutamate release. This effect was reversed by application of the putative galanin receptor antagonist M35. These data provide evidence that ectopically overexpressed galanin can be released and dampen the development of epilepsy by means of receptor-mediated action, at least partly by reducing glutamate release from mossy fibers.},
  author       = {Kokaia, Merab and Holmberg, Kristina and Nanobashvili, Avtandil and Xu, Zhi-Qing D. and Kokaia, Zaal and Lendahl, Urban and Hilke, Susanne and Theodorsson, Elvar and Kahl, Ulrika and Bartfai, Tamas and Lindvall, Olle and Hökfelt, Tomas},
  issn         = {1091-6490},
  language     = {eng},
  number       = {24},
  pages        = {14006--14011},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Suppressed kindling epileptogenesis in mice with ectopic overexpression of galanin},
  url          = {http://dx.doi.org/10.1073/pnas.231496298},
  volume       = {98},
  year         = {2001},
}