Publication

North Sea Progressive Myoclonus Epilepsy is Exacerbated by Heat, A Phenotype Primarily Associated with Affected Glia

Lambrechts, R. A., Polet, S. S., Hernandez-Pichardo, A., van Ninhuys, L., Gorter, J. A., Grzeschik, N. A., de Koning-Tijssen, M. A. J., de Koning, T. J. & Sibon, O. C. M., 15-Dec-2019, In : Neuroscience. 423, p. 1-11 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Lambrechts, R. A., Polet, S. S., Hernandez-Pichardo, A., van Ninhuys, L., Gorter, J. A., Grzeschik, N. A., de Koning-Tijssen, M. A. J., de Koning, T. J., & Sibon, O. C. M. (2019). North Sea Progressive Myoclonus Epilepsy is Exacerbated by Heat, A Phenotype Primarily Associated with Affected Glia. Neuroscience, 423, 1-11. https://doi.org/10.1016/j.neuroscience.2019.10.035

Author

Lambrechts, Roald A ; Polet, Sjoukje S ; Hernandez-Pichardo, Alejandra ; van Ninhuys, Lisa ; Gorter, Jenke A ; Grzeschik, Nicola A ; de Koning-Tijssen, Marina A J ; de Koning, Tom J ; Sibon, Ody C M. / North Sea Progressive Myoclonus Epilepsy is Exacerbated by Heat, A Phenotype Primarily Associated with Affected Glia. In: Neuroscience. 2019 ; Vol. 423. pp. 1-11.

Harvard

Lambrechts, RA, Polet, SS, Hernandez-Pichardo, A, van Ninhuys, L, Gorter, JA, Grzeschik, NA, de Koning-Tijssen, MAJ, de Koning, TJ & Sibon, OCM 2019, 'North Sea Progressive Myoclonus Epilepsy is Exacerbated by Heat, A Phenotype Primarily Associated with Affected Glia', Neuroscience, vol. 423, pp. 1-11. https://doi.org/10.1016/j.neuroscience.2019.10.035

Standard

North Sea Progressive Myoclonus Epilepsy is Exacerbated by Heat, A Phenotype Primarily Associated with Affected Glia. / Lambrechts, Roald A; Polet, Sjoukje S; Hernandez-Pichardo, Alejandra; van Ninhuys, Lisa; Gorter, Jenke A; Grzeschik, Nicola A; de Koning-Tijssen, Marina A J; de Koning, Tom J; Sibon, Ody C M.

In: Neuroscience, Vol. 423, 15.12.2019, p. 1-11.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Lambrechts RA, Polet SS, Hernandez-Pichardo A, van Ninhuys L, Gorter JA, Grzeschik NA et al. North Sea Progressive Myoclonus Epilepsy is Exacerbated by Heat, A Phenotype Primarily Associated with Affected Glia. Neuroscience. 2019 Dec 15;423:1-11. https://doi.org/10.1016/j.neuroscience.2019.10.035


BibTeX

@article{9ead118c2c0140a7bdc20958c6ea2fce,
title = "North Sea Progressive Myoclonus Epilepsy is Exacerbated by Heat, A Phenotype Primarily Associated with Affected Glia",
abstract = "Progressive myoclonic epilepsies (PMEs) comprise a group of rare disorders of different genetic aetiologies, leading to childhood-onset myoclonus, myoclonic seizures and subsequent neurological decline. One of the genetic causes for PME, a mutation in the gene coding for Golgi SNAP receptor 2 (GOSR2), gives rise to a PME-subtype prevalent in Northern Europe and hence referred to as North Sea Progressive Myoclonic Epilepsy (NS-PME). Treatment for NS-PME, as for all PME subtypes, is symptomatic; the pathophysiology of NS-PME is currently unknown, precluding targeted therapy. Here, we investigated the pathophysiology of NS-PME. By means of chart review in combination with interviews with patients (n = 14), we found heat to be an exacerbating factor for a majority of NS-PME patients (86%). To substantiate these findings, we designed a NS-PME Drosophila melanogaster model. Downregulation of the Drosophila GOSR2-orthologue Membrin leads to heat-induced seizure-like behaviour. Specific downregulation of GOSR2/Membrin in glia but not in neuronal cells resulted in a similar phenotype, which was progressive as the flies aged and was partially responsive to treatment with sodium barbital. Our data suggest a role for GOSR2 in glia in the pathophysiology of NS-PME. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.",
keywords = "myoclonic epilepsy, childhood onset, GOSR2, glia, DROSOPHILA, SEIZURE, ANTICONVULSANT, MUTATION, ATAXIA, MODEL",
author = "Lambrechts, {Roald A} and Polet, {Sjoukje S} and Alejandra Hernandez-Pichardo and {van Ninhuys}, Lisa and Gorter, {Jenke A} and Grzeschik, {Nicola A} and {de Koning-Tijssen}, {Marina A J} and {de Koning}, {Tom J} and Sibon, {Ody C M}",
note = "Copyright {\textcopyright} 2019 IBRO. Published by Elsevier Ltd. All rights reserved.",
year = "2019",
month = dec,
day = "15",
doi = "10.1016/j.neuroscience.2019.10.035",
language = "English",
volume = "423",
pages = "1--11",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "PERGAMON-ELSEVIER SCIENCE LTD",

}

RIS

TY - JOUR

T1 - North Sea Progressive Myoclonus Epilepsy is Exacerbated by Heat, A Phenotype Primarily Associated with Affected Glia

AU - Lambrechts, Roald A

AU - Polet, Sjoukje S

AU - Hernandez-Pichardo, Alejandra

AU - van Ninhuys, Lisa

AU - Gorter, Jenke A

AU - Grzeschik, Nicola A

AU - de Koning-Tijssen, Marina A J

AU - de Koning, Tom J

AU - Sibon, Ody C M

N1 - Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

PY - 2019/12/15

Y1 - 2019/12/15

N2 - Progressive myoclonic epilepsies (PMEs) comprise a group of rare disorders of different genetic aetiologies, leading to childhood-onset myoclonus, myoclonic seizures and subsequent neurological decline. One of the genetic causes for PME, a mutation in the gene coding for Golgi SNAP receptor 2 (GOSR2), gives rise to a PME-subtype prevalent in Northern Europe and hence referred to as North Sea Progressive Myoclonic Epilepsy (NS-PME). Treatment for NS-PME, as for all PME subtypes, is symptomatic; the pathophysiology of NS-PME is currently unknown, precluding targeted therapy. Here, we investigated the pathophysiology of NS-PME. By means of chart review in combination with interviews with patients (n = 14), we found heat to be an exacerbating factor for a majority of NS-PME patients (86%). To substantiate these findings, we designed a NS-PME Drosophila melanogaster model. Downregulation of the Drosophila GOSR2-orthologue Membrin leads to heat-induced seizure-like behaviour. Specific downregulation of GOSR2/Membrin in glia but not in neuronal cells resulted in a similar phenotype, which was progressive as the flies aged and was partially responsive to treatment with sodium barbital. Our data suggest a role for GOSR2 in glia in the pathophysiology of NS-PME. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

AB - Progressive myoclonic epilepsies (PMEs) comprise a group of rare disorders of different genetic aetiologies, leading to childhood-onset myoclonus, myoclonic seizures and subsequent neurological decline. One of the genetic causes for PME, a mutation in the gene coding for Golgi SNAP receptor 2 (GOSR2), gives rise to a PME-subtype prevalent in Northern Europe and hence referred to as North Sea Progressive Myoclonic Epilepsy (NS-PME). Treatment for NS-PME, as for all PME subtypes, is symptomatic; the pathophysiology of NS-PME is currently unknown, precluding targeted therapy. Here, we investigated the pathophysiology of NS-PME. By means of chart review in combination with interviews with patients (n = 14), we found heat to be an exacerbating factor for a majority of NS-PME patients (86%). To substantiate these findings, we designed a NS-PME Drosophila melanogaster model. Downregulation of the Drosophila GOSR2-orthologue Membrin leads to heat-induced seizure-like behaviour. Specific downregulation of GOSR2/Membrin in glia but not in neuronal cells resulted in a similar phenotype, which was progressive as the flies aged and was partially responsive to treatment with sodium barbital. Our data suggest a role for GOSR2 in glia in the pathophysiology of NS-PME. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

KW - myoclonic epilepsy

KW - childhood onset

KW - GOSR2

KW - glia

KW - DROSOPHILA

KW - SEIZURE

KW - ANTICONVULSANT

KW - MUTATION

KW - ATAXIA

KW - MODEL

U2 - 10.1016/j.neuroscience.2019.10.035

DO - 10.1016/j.neuroscience.2019.10.035

M3 - Article

C2 - 31682953

VL - 423

SP - 1

EP - 11

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

ER -

ID: 101549859