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Inhibition of epileptiform activity by neuropeptide Y in brain tissue from drug-resistant temporal lobe epilepsy patients

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Wickham, Jenny ; Ledri, Marco ; Bengzon, Johan ; Jespersen, Bo ; Pinborg, Lars H ; Englund, Elisabet ; Woldbye, David P D ; Andersson, My ; Kokaia, Merab. / Inhibition of epileptiform activity by neuropeptide Y in brain tissue from drug-resistant temporal lobe epilepsy patients. I: Scientific Reports. 2019 ; Bind 9, Nr. 1. s. 19393.

Bibtex

@article{6191523aeeaa46fba2240edaf1c8135c,
title = "Inhibition of epileptiform activity by neuropeptide Y in brain tissue from drug-resistant temporal lobe epilepsy patients",
abstract = "In epilepsy patients, drug-resistant seizures often originate in one of the temporal lobes. In selected cases, when certain requirements are met, this area is surgically resected for therapeutic reasons. We kept the resected tissue slices alive in vitro for 48 h to create a platform for testing a novel treatment strategy based on neuropeptide Y (NPY) against drug-resistant epilepsy. We demonstrate that NPY exerts a significant inhibitory effect on epileptiform activity, recorded with whole-cell patch-clamp, in human hippocampal dentate gyrus. Application of NPY reduced overall number of paroxysmal depolarising shifts and action potentials. This effect was mediated by Y2 receptors, since application of selective Y2-receptor antagonist blocked the effect of NPY. This proof-of-concept finding is an important translational milestone for validating NPY-based gene therapy for targeting focal drug-resistant epilepsies, and increasing the prospects for positive outcome in potential clinical trials.",
author = "Jenny Wickham and Marco Ledri and Johan Bengzon and Bo Jespersen and Pinborg, {Lars H} and Elisabet Englund and Woldbye, {David P D} and My Andersson and Merab Kokaia",
year = "2019",
month = "12",
day = "18",
doi = "10.1038/s41598-019-56062-1",
language = "English",
volume = "9",
pages = "19393",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Inhibition of epileptiform activity by neuropeptide Y in brain tissue from drug-resistant temporal lobe epilepsy patients

AU - Wickham, Jenny

AU - Ledri, Marco

AU - Bengzon, Johan

AU - Jespersen, Bo

AU - Pinborg, Lars H

AU - Englund, Elisabet

AU - Woldbye, David P D

AU - Andersson, My

AU - Kokaia, Merab

PY - 2019/12/18

Y1 - 2019/12/18

N2 - In epilepsy patients, drug-resistant seizures often originate in one of the temporal lobes. In selected cases, when certain requirements are met, this area is surgically resected for therapeutic reasons. We kept the resected tissue slices alive in vitro for 48 h to create a platform for testing a novel treatment strategy based on neuropeptide Y (NPY) against drug-resistant epilepsy. We demonstrate that NPY exerts a significant inhibitory effect on epileptiform activity, recorded with whole-cell patch-clamp, in human hippocampal dentate gyrus. Application of NPY reduced overall number of paroxysmal depolarising shifts and action potentials. This effect was mediated by Y2 receptors, since application of selective Y2-receptor antagonist blocked the effect of NPY. This proof-of-concept finding is an important translational milestone for validating NPY-based gene therapy for targeting focal drug-resistant epilepsies, and increasing the prospects for positive outcome in potential clinical trials.

AB - In epilepsy patients, drug-resistant seizures often originate in one of the temporal lobes. In selected cases, when certain requirements are met, this area is surgically resected for therapeutic reasons. We kept the resected tissue slices alive in vitro for 48 h to create a platform for testing a novel treatment strategy based on neuropeptide Y (NPY) against drug-resistant epilepsy. We demonstrate that NPY exerts a significant inhibitory effect on epileptiform activity, recorded with whole-cell patch-clamp, in human hippocampal dentate gyrus. Application of NPY reduced overall number of paroxysmal depolarising shifts and action potentials. This effect was mediated by Y2 receptors, since application of selective Y2-receptor antagonist blocked the effect of NPY. This proof-of-concept finding is an important translational milestone for validating NPY-based gene therapy for targeting focal drug-resistant epilepsies, and increasing the prospects for positive outcome in potential clinical trials.

U2 - 10.1038/s41598-019-56062-1

DO - 10.1038/s41598-019-56062-1

M3 - Journal article

VL - 9

SP - 19393

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

ER -

ID: 58940603