North Sea Progressive Myoclonus Epilepsy is Exacerbated by Heat, A Phenotype Primarily Associated with Affected Glia
(2019) In Neuroscience 423. p.1-11- 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... (More)
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.
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- 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. LU and Sibon, Ody C.M.
- publishing date
- 2019-12-15
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- childhood onset, glia, GOSR2, myoclonic epilepsy
- in
- Neuroscience
- volume
- 423
- pages
- 11 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:31682953
- scopus:85074759306
- ISSN
- 0306-4522
- DOI
- 10.1016/j.neuroscience.2019.10.035
- language
- English
- LU publication?
- no
- id
- 0649cea1-56e4-44f7-8fab-b77c2d4743dc
- date added to LUP
- 2020-01-28 09:47:12
- date last changed
- 2024-09-18 18:10:41
@article{0649cea1-56e4-44f7-8fab-b77c2d4743dc, abstract = {{<p>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.</p>}}, author = {{Lambrechts, Roald A. and Polet, Sjoukje S. and Hernandez-Pichardo, Alejandra 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.}}, issn = {{0306-4522}}, keywords = {{childhood onset; glia; GOSR2; myoclonic epilepsy}}, language = {{eng}}, month = {{12}}, pages = {{1--11}}, publisher = {{Elsevier}}, series = {{Neuroscience}}, title = {{North Sea Progressive Myoclonus Epilepsy is Exacerbated by Heat, A Phenotype Primarily Associated with Affected Glia}}, url = {{http://dx.doi.org/10.1016/j.neuroscience.2019.10.035}}, doi = {{10.1016/j.neuroscience.2019.10.035}}, volume = {{423}}, year = {{2019}}, }