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Galanin gene transfer curtails generalized seizures in kindled rats without altering hippocampal synaptic plasticity

Kanter Schlifke, Irene LU ; Toft Sörensen, Andreas LU ; Ledri, Marco LU ; Kuteeva, E; Hokfelt, T and Kokaia, Merab LU (2007) In Neuroscience 150(4). p.984-992
Abstract
Gene therapy-based overexpression of endogenous seizure-suppressing molecules represents a promising treatment strategy for epilepsy. Viral vector-based overexpression of the neuropeptide galanin has been shown to effectively suppress generalized seizures in various animal models of epilepsy. However, it has not been explored whether such treatment can also prevent the epileptogenesis. Using a recombinant adeno-associated viral (rAAV) vector, we induced hippocampal galanin overexpression under the neuron specific enolase promoter in rats. Here we report that in animals with galanin overexpression, the duration of electrographic afterdischarges was shortened and initiation of convulsions was delayed at generalized seizure stages. However,... (More)
Gene therapy-based overexpression of endogenous seizure-suppressing molecules represents a promising treatment strategy for epilepsy. Viral vector-based overexpression of the neuropeptide galanin has been shown to effectively suppress generalized seizures in various animal models of epilepsy. However, it has not been explored whether such treatment can also prevent the epileptogenesis. Using a recombinant adeno-associated viral (rAAV) vector, we induced hippocampal galanin overexpression under the neuron specific enolase promoter in rats. Here we report that in animals with galanin overexpression, the duration of electrographic afterdischarges was shortened and initiation of convulsions was delayed at generalized seizure stages. However, the hippocampal kindling development was unchanged. Short-term plasticity of mossy fiber-cornu ammonis (CA) 3 synapses was unaltered, as assessed by paired-pulse and frequency facilitation of field excitatory postsynaptic potentials (fEPSPs) in hippocampal slices, suggesting that despite high transgene galanin expression, overall release probability of glutamate in these synapses was unaffected. These data indicate that hippocampal rAAV-based galanin overexpression is capable of mediating anticonvulsant effects by lowering the seizure susceptibility once generalized seizures are induced, but does not seem to affect kindling development or presynaptic short-term plasticity in mossy fibers. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neuroscience
volume
150
issue
4
pages
984 - 992
publisher
Elsevier
external identifiers
  • pmid:17988802
  • wos:000251863100023
  • scopus:37049010150
ISSN
1873-7544
DOI
10.1016/j.neuroscience.2007.09.056
language
English
LU publication?
yes
id
be756c93-67f6-4a86-b784-9b2bcdf3bdb0 (old id 1141382)
date added to LUP
2008-08-12 14:27:49
date last changed
2017-02-26 04:21:32
@article{be756c93-67f6-4a86-b784-9b2bcdf3bdb0,
  abstract     = {Gene therapy-based overexpression of endogenous seizure-suppressing molecules represents a promising treatment strategy for epilepsy. Viral vector-based overexpression of the neuropeptide galanin has been shown to effectively suppress generalized seizures in various animal models of epilepsy. However, it has not been explored whether such treatment can also prevent the epileptogenesis. Using a recombinant adeno-associated viral (rAAV) vector, we induced hippocampal galanin overexpression under the neuron specific enolase promoter in rats. Here we report that in animals with galanin overexpression, the duration of electrographic afterdischarges was shortened and initiation of convulsions was delayed at generalized seizure stages. However, the hippocampal kindling development was unchanged. Short-term plasticity of mossy fiber-cornu ammonis (CA) 3 synapses was unaltered, as assessed by paired-pulse and frequency facilitation of field excitatory postsynaptic potentials (fEPSPs) in hippocampal slices, suggesting that despite high transgene galanin expression, overall release probability of glutamate in these synapses was unaffected. These data indicate that hippocampal rAAV-based galanin overexpression is capable of mediating anticonvulsant effects by lowering the seizure susceptibility once generalized seizures are induced, but does not seem to affect kindling development or presynaptic short-term plasticity in mossy fibers.},
  author       = {Kanter Schlifke, Irene and Toft Sörensen, Andreas and Ledri, Marco and Kuteeva, E and Hokfelt, T and Kokaia, Merab},
  issn         = {1873-7544},
  language     = {eng},
  number       = {4},
  pages        = {984--992},
  publisher    = {Elsevier},
  series       = {Neuroscience},
  title        = {Galanin gene transfer curtails generalized seizures in kindled rats without altering hippocampal synaptic plasticity},
  url          = {http://dx.doi.org/10.1016/j.neuroscience.2007.09.056},
  volume       = {150},
  year         = {2007},
}