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Hippocampal NPY gene transfer attenuates seizures without affecting epilepsy-induced impairment of LTP.

Toft Sörensen, Andreas LU ; Nikitidou, Litsa LU ; Ledri, Marco LU ; Lin, En-Ju D; During, Matthew J; Kanter Schlifke, Irene LU and Kokaia, Merab LU (2009) In Experimental Neurology 215. p.328-333
Abstract
Recently, hippocampal neuropeptide Y (NPY) gene therapy has been shown to effectively suppress both acute and chronic seizures in animal model of epilepsy, thus representing a promising novel antiepileptic treatment strategy, particularly for patients with intractable mesial temporal lobe epilepsy (TLE). However, our previous studies show that recombinant adeno-associated viral (rAAV)-NPY treatment in naive rats attenuates long-term potentiation (LTP) and transiently impairs hippocampal learning process, indicating that negative effect on memory function could be a potential side effect of NPY gene therapy. Here we report how rAAV vector-mediated overexpression of NPY in the hippocampus affects rapid kindling, and subsequently explore how... (More)
Recently, hippocampal neuropeptide Y (NPY) gene therapy has been shown to effectively suppress both acute and chronic seizures in animal model of epilepsy, thus representing a promising novel antiepileptic treatment strategy, particularly for patients with intractable mesial temporal lobe epilepsy (TLE). However, our previous studies show that recombinant adeno-associated viral (rAAV)-NPY treatment in naive rats attenuates long-term potentiation (LTP) and transiently impairs hippocampal learning process, indicating that negative effect on memory function could be a potential side effect of NPY gene therapy. Here we report how rAAV vector-mediated overexpression of NPY in the hippocampus affects rapid kindling, and subsequently explore how synaptic plasticity and transmission is affected by kindling and NPY overexpression by field recordings in CA1 stratum radiatum of brain slices. In animals injected with rAAV-NPY, we show that rapid kindling-induced hippocampal seizures in vivo are effectively suppressed as compared to rAAV-empty injected (control) rats. Six to nine weeks later, basal synaptic transmission and short-term synaptic plasticity are unchanged after rapid kindling, while LTP is significantly attenuated in vitro. Importantly, transgene NPY overexpression has no effect on short-term synaptic plasticity, and does not further compromise LTP in kindled animals. These data suggest that epileptic seizure-induced impairment of memory function in the hippocampus may not be further affected by rAAV-NPY treatment, and may be considered less critical for clinical application in epilepsy patients already experiencing memory disturbances. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Experimental Neurology
volume
215
pages
328 - 333
publisher
Academic Press
external identifiers
  • wos:000262890900015
  • pmid:19038255
  • scopus:58249106738
ISSN
0014-4886
DOI
10.1016/j.expneurol.2008.10.015
language
English
LU publication?
yes
id
ce64df65-1b2c-479f-9219-27042bc998d9 (old id 1271020)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19038255?dopt=Abstract
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2896682/
http://www.sciencedirect.com/science/article/pii/S0014488608004135
date added to LUP
2008-12-03 13:19:20
date last changed
2017-02-26 04:22:17
@article{ce64df65-1b2c-479f-9219-27042bc998d9,
  abstract     = {Recently, hippocampal neuropeptide Y (NPY) gene therapy has been shown to effectively suppress both acute and chronic seizures in animal model of epilepsy, thus representing a promising novel antiepileptic treatment strategy, particularly for patients with intractable mesial temporal lobe epilepsy (TLE). However, our previous studies show that recombinant adeno-associated viral (rAAV)-NPY treatment in naive rats attenuates long-term potentiation (LTP) and transiently impairs hippocampal learning process, indicating that negative effect on memory function could be a potential side effect of NPY gene therapy. Here we report how rAAV vector-mediated overexpression of NPY in the hippocampus affects rapid kindling, and subsequently explore how synaptic plasticity and transmission is affected by kindling and NPY overexpression by field recordings in CA1 stratum radiatum of brain slices. In animals injected with rAAV-NPY, we show that rapid kindling-induced hippocampal seizures in vivo are effectively suppressed as compared to rAAV-empty injected (control) rats. Six to nine weeks later, basal synaptic transmission and short-term synaptic plasticity are unchanged after rapid kindling, while LTP is significantly attenuated in vitro. Importantly, transgene NPY overexpression has no effect on short-term synaptic plasticity, and does not further compromise LTP in kindled animals. These data suggest that epileptic seizure-induced impairment of memory function in the hippocampus may not be further affected by rAAV-NPY treatment, and may be considered less critical for clinical application in epilepsy patients already experiencing memory disturbances.},
  author       = {Toft Sörensen, Andreas and Nikitidou, Litsa and Ledri, Marco and Lin, En-Ju D and During, Matthew J and Kanter Schlifke, Irene and Kokaia, Merab},
  issn         = {0014-4886},
  language     = {eng},
  pages        = {328--333},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {Hippocampal NPY gene transfer attenuates seizures without affecting epilepsy-induced impairment of LTP.},
  url          = {http://dx.doi.org/10.1016/j.expneurol.2008.10.015},
  volume       = {215},
  year         = {2009},
}