Differential Effect of Neuropeptides on Excitatory Synaptic Transmission in Human Epileptic Hippocampus.
(2015) In The 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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/7751025
- author
- 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
; Jespersen, Bo
; Gøtzsche, Casper R
; Woldbye, David P D
; Andersson, My
LU
and Kokaia, Merab
LU
(Less) - organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- The Journal of Neuroscience
- volume
- 35
- issue
- 26
- pages
- 9622 - 9631
- publisher
- Society for Neuroscience
- external identifiers
-
- pmid:26134645
- wos:000358252600010
- scopus:84936141748
- pmid:26134645
- ISSN
- 1529-2401
- DOI
- 10.1523/JNEUROSCI.3973-14.2015
- language
- English
- LU publication?
- yes
- id
- 7935cd74-94e6-4639-8b98-00aa6c216c9f (old id 7751025)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/26134645?dopt=Abstract
- date added to LUP
- 2016-04-01 10:14:48
- date last changed
- 2023-10-11 23:30:35
@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 = {{The Journal of Neuroscience}},
title = {{Differential Effect of Neuropeptides on Excitatory Synaptic Transmission in Human Epileptic Hippocampus.}},
url = {{https://lup.lub.lu.se/search/files/1686753/8596697.pdf}},
doi = {{10.1523/JNEUROSCI.3973-14.2015}},
volume = {{35}},
year = {{2015}},
}