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

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Harvard

Ledri, M, Sørensen, AT, Madsen, MG, Christiansen, SH, Ledri, LN, Cifra, A, Bengzon, J, Lindberg, E, Pinborg, LH, Jespersen, B, Gøtzsche, CR, Woldbye, DPD, Andersson, M & Kokaia, M 2015, 'Differential Effect of Neuropeptides on Excitatory Synaptic Transmission in Human Epileptic Hippocampus', The Journal of Neuroscience : the official journal of the Society for Neuroscience, vol. 35, no. 26, pp. 9622-31. https://doi.org/10.1523/JNEUROSCI.3973-14.2015

APA

Ledri, M., Sørensen, A. T., Madsen, M. G., Christiansen, S. H., Ledri, L. N., Cifra, A., Bengzon, J., Lindberg, E., Pinborg, L. H., Jespersen, B., Gøtzsche, C. R., Woldbye, D. P. D., Andersson, M., & Kokaia, M. (2015). Differential Effect of Neuropeptides on Excitatory Synaptic Transmission in Human Epileptic Hippocampus. The Journal of Neuroscience : the official journal of the Society for Neuroscience, 35(26), 9622-31. https://doi.org/10.1523/JNEUROSCI.3973-14.2015

CBE

MLA

Vancouver

Author

Ledri, Marco ; Sørensen, Andreas T ; Madsen, Marita G ; Christiansen, Søren H ; Ledri, Litsa Nikitidou ; Cifra, Alessandra ; Bengzon, Johan ; Lindberg, Eva ; Pinborg, Lars H ; Jespersen, Bo ; Gøtzsche, Casper R ; Woldbye, David P D ; Andersson, My ; Kokaia, Merab. / Differential Effect of Neuropeptides on Excitatory Synaptic Transmission in Human Epileptic Hippocampus. In: The Journal of Neuroscience : the official journal of the Society for Neuroscience. 2015 ; Vol. 35, No. 26. pp. 9622-31.

Bibtex

@article{c6f532ec2fc441199256a94221590e63,
title = "Differential Effect of Neuropeptides on Excitatory Synaptic Transmission in Human Epileptic Hippocampus",
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.",
keywords = "Adolescent, Adult, Epilepsy, Excitatory Postsynaptic Potentials, Female, Galanin, Guanosine 5'-O-(3-Thiotriphosphate), Hippocampus, Humans, In Vitro Techniques, Male, Membrane Potentials, Microtubule-Associated Proteins, Middle Aged, Neuropeptide Y, Patch-Clamp Techniques, Radioligand Assay, Receptors, Galanin, Receptors, Neuropeptide Y, Sulfur Isotopes, Synapses, Synaptic Transmission, Young Adult",
author = "Marco Ledri and S{\o}rensen, {Andreas T} and Madsen, {Marita G} and Christiansen, {S{\o}ren H} and Ledri, {Litsa Nikitidou} and Alessandra Cifra and Johan Bengzon and Eva Lindberg and Pinborg, {Lars H} and Bo Jespersen and G{\o}tzsche, {Casper R} and Woldbye, {David P D} and My Andersson and Merab Kokaia",
note = "Copyright {\textcopyright} 2015 the authors 0270-6474/15/359622-10$15.00/0.",
year = "2015",
month = jul,
day = "1",
doi = "10.1523/JNEUROSCI.3973-14.2015",
language = "English",
volume = "35",
pages = "9622--31",
journal = "Neuroscience Journal",
issn = "2314-4262",
publisher = "Hindawi Publishing Corporation",
number = "26",

}

RIS

TY - JOUR

T1 - Differential Effect of Neuropeptides on Excitatory Synaptic Transmission in Human Epileptic Hippocampus

AU - Ledri, Marco

AU - Sørensen, Andreas T

AU - Madsen, Marita G

AU - Christiansen, Søren H

AU - Ledri, Litsa Nikitidou

AU - Cifra, Alessandra

AU - Bengzon, Johan

AU - Lindberg, Eva

AU - Pinborg, Lars H

AU - Jespersen, Bo

AU - Gøtzsche, Casper R

AU - Woldbye, David P D

AU - Andersson, My

AU - Kokaia, Merab

N1 - Copyright © 2015 the authors 0270-6474/15/359622-10$15.00/0.

PY - 2015/7/1

Y1 - 2015/7/1

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Epilepsy

KW - Excitatory Postsynaptic Potentials

KW - Female

KW - Galanin

KW - Guanosine 5'-O-(3-Thiotriphosphate)

KW - Hippocampus

KW - Humans

KW - In Vitro Techniques

KW - Male

KW - Membrane Potentials

KW - Microtubule-Associated Proteins

KW - Middle Aged

KW - Neuropeptide Y

KW - Patch-Clamp Techniques

KW - Radioligand Assay

KW - Receptors, Galanin

KW - Receptors, Neuropeptide Y

KW - Sulfur Isotopes

KW - Synapses

KW - Synaptic Transmission

KW - Young Adult

U2 - 10.1523/JNEUROSCI.3973-14.2015

DO - 10.1523/JNEUROSCI.3973-14.2015

M3 - Journal article

C2 - 26134645

VL - 35

SP - 9622

EP - 9631

JO - Neuroscience Journal

JF - Neuroscience Journal

SN - 2314-4262

IS - 26

ER -

ID: 45644108