Inhibition of epileptiform activity by neuropeptide Y in brain tissue from drug-resistant temporal lobe epilepsy patients
(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
- Wickham, Jenny LU ; Ledri, Marco LU ; Bengzon, Johan LU ; Jespersen, Bo ; Pinborg, Lars H. ; Englund, Elisabet LU ; Woldbye, David P.D. ; Andersson, My LU and Kokaia, Merab LU
- organization
-
- Experimental Epilepsy Group (research group)
- Neurosurgery
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
- Tumor microenvironment
- MultiPark: Multidisciplinary research focused on ParkinsonĀ“s disease
- Epilepsy Center
- Cellular Neurophysiology and Epilepsy group (research group)
- NanoLund: Centre for Nanoscience
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 9
- issue
- 1
- article number
- 19393
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:31852985
- scopus:85076748084
- 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
- 2024-07-25 12:12:21
@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}}, }