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Differential Effect of Neuropeptides on Excitatory Synaptic Transmission in Human Epileptic Hippocampus.

Ledri, Marco LU ; Sørensen, Andreas T; Grönning Madsen, Marita LU ; Christiansen, Søren H; Ledri, Litsa Nikitidou; Cifra, Alessandra LU ; Bengzon, Johan LU ; Lindberg, Eva; Pinborg, Lars H and Jespersen, Bo, et al. (2015) In Journal of Neuroscience 35(26). p.9622-9631
Abstract
Development of novel disease-modifying treatment strategies for neurological disorders, which at present have no cure, represents a major challenge for today's neurology. Translation of findings from animal models to humans represents an unresolved gap in most of the preclinical studies. Gene therapy is an evolving innovative approach that may prove useful for clinical applications. In animal models of temporal lobe epilepsy (TLE), gene therapy treatments based on viral vectors encoding NPY or galanin have been shown to effectively suppress seizures. However, how this translates to human TLE remains unknown. A unique possibility to validate these animal studies is provided by a surgical therapeutic approach, whereby resected epileptic... (More)
Development of novel disease-modifying treatment strategies for neurological disorders, which at present have no cure, represents a major challenge for today's neurology. Translation of findings from animal models to humans represents an unresolved gap in most of the preclinical studies. Gene therapy is an evolving innovative approach that may prove useful for clinical applications. In animal models of temporal lobe epilepsy (TLE), gene therapy treatments based on viral vectors encoding NPY or galanin have been shown to effectively suppress seizures. However, how this translates to human TLE remains unknown. A unique possibility to validate these animal studies is provided by a surgical therapeutic approach, whereby resected epileptic tissue from temporal lobes of pharmacoresistant patients are available for neurophysiological studies in vitro. To test whether NPY and galanin have antiepileptic actions in human epileptic tissue as well, we applied these neuropeptides directly to human hippocampal slices in vitro. NPY strongly decreased stimulation-induced EPSPs in dentate gyrus and CA1 (up to 30 and 55%, respectively) via Y2 receptors, while galanin had no significant effect. Receptor autoradiographic binding revealed the presence of both NPY and galanin receptors, while functional receptor binding was only detected for NPY, suggesting that galanin receptor signaling may be impaired. These results underline the importance of validating findings from animal studies in human brain tissue, and advocate for NPY as a more appropriate candidate than galanin for future gene therapy trials in pharmacoresistant TLE patients. (Less)
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published
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Journal of Neuroscience
volume
35
issue
26
pages
9622 - 9631
publisher
Society for Neuroscience
external identifiers
  • pmid:26134645
  • wos:000358252600010
  • scopus:84936141748
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.3973-14.2015
language
English
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yes
id
7935cd74-94e6-4639-8b98-00aa6c216c9f (old id 7751025)
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http://www.ncbi.nlm.nih.gov/pubmed/26134645?dopt=Abstract
date added to LUP
2015-08-04 20:44:49
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2017-09-19 14:58:14
@article{7935cd74-94e6-4639-8b98-00aa6c216c9f,
  abstract     = {Development of novel disease-modifying treatment strategies for neurological disorders, which at present have no cure, represents a major challenge for today's neurology. Translation of findings from animal models to humans represents an unresolved gap in most of the preclinical studies. Gene therapy is an evolving innovative approach that may prove useful for clinical applications. In animal models of temporal lobe epilepsy (TLE), gene therapy treatments based on viral vectors encoding NPY or galanin have been shown to effectively suppress seizures. However, how this translates to human TLE remains unknown. A unique possibility to validate these animal studies is provided by a surgical therapeutic approach, whereby resected epileptic tissue from temporal lobes of pharmacoresistant patients are available for neurophysiological studies in vitro. To test whether NPY and galanin have antiepileptic actions in human epileptic tissue as well, we applied these neuropeptides directly to human hippocampal slices in vitro. NPY strongly decreased stimulation-induced EPSPs in dentate gyrus and CA1 (up to 30 and 55%, respectively) via Y2 receptors, while galanin had no significant effect. Receptor autoradiographic binding revealed the presence of both NPY and galanin receptors, while functional receptor binding was only detected for NPY, suggesting that galanin receptor signaling may be impaired. These results underline the importance of validating findings from animal studies in human brain tissue, and advocate for NPY as a more appropriate candidate than galanin for future gene therapy trials in pharmacoresistant TLE patients.},
  author       = {Ledri, Marco and Sørensen, Andreas T and Grönning Madsen, Marita and Christiansen, Søren H and Ledri, Litsa Nikitidou and Cifra, Alessandra and Bengzon, Johan and Lindberg, Eva and Pinborg, Lars H and Jespersen, Bo and Gøtzsche, Casper R and Woldbye, David P D and Andersson, My and Kokaia, Merab},
  issn         = {1529-2401},
  language     = {eng},
  number       = {26},
  pages        = {9622--9631},
  publisher    = {Society for Neuroscience},
  series       = {Journal of Neuroscience},
  title        = {Differential Effect of Neuropeptides on Excitatory Synaptic Transmission in Human Epileptic Hippocampus.},
  url          = {http://dx.doi.org/10.1523/JNEUROSCI.3973-14.2015},
  volume       = {35},
  year         = {2015},
}