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

Wickham, Jenny LU orcid ; Ledri, Marco LU ; Bengzon, Johan LU ; Jespersen, Bo ; Pinborg, Lars H. ; Englund, Elisabet LU orcid ; Woldbye, David P.D. ; Andersson, My LU orcid and Kokaia, Merab LU (2019) In Scientific Reports 9(1).
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... (More)

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.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
9
issue
1
article number
19393
publisher
Nature Publishing Group
external identifiers
  • scopus:85076748084
  • pmid:31852985
ISSN
2045-2322
DOI
10.1038/s41598-019-56062-1
language
English
LU publication?
yes
id
69df5f5b-c695-4b61-ad48-49720063713b
date added to LUP
2020-01-07 14:42:21
date last changed
2024-06-26 09:09:18
@article{69df5f5b-c695-4b61-ad48-49720063713b,
  abstract     = {{<p>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.</p>}},
  author       = {{Wickham, Jenny and Ledri, Marco and Bengzon, Johan and Jespersen, Bo and Pinborg, Lars H. and Englund, Elisabet and Woldbye, David P.D. and Andersson, My and Kokaia, Merab}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Inhibition of epileptiform activity by neuropeptide Y in brain tissue from drug-resistant temporal lobe epilepsy patients}},
  url          = {{http://dx.doi.org/10.1038/s41598-019-56062-1}},
  doi          = {{10.1038/s41598-019-56062-1}},
  volume       = {{9}},
  year         = {{2019}},
}