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Important role of matrix metalloproteinase 9 in epileptogenesis
Temporal lobe epilepsy (TLE) is a devastating disease in which aberrant synaptic plasticity plays a major role. We identify matrix metalloproteinase (MMP) 9 as a novel synaptic enzyme and a key pathogenic factor in two animal models of TLE: kainate-evoked epilepsy and pentylenetetrazole (PTZ) kindli...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265409/ https://www.ncbi.nlm.nih.gov/pubmed/18332222 http://dx.doi.org/10.1083/jcb.200708213 |
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author | Wilczynski, Grzegorz M. Konopacki, Filip A. Wilczek, Ewa Lasiecka, Zofia Gorlewicz, Adam Michaluk, Piotr Wawrzyniak, Marcin Malinowska, Monika Okulski, Pawel Kolodziej, Lukasz R. Konopka, Witold Duniec, Kamila Mioduszewska, Barbara Nikolaev, Evgeni Walczak, Agnieszka Owczarek, Dorota Gorecki, Dariusz C. Zuschratter, Werner Ottersen, Ole Petter Kaczmarek, Leszek |
author_facet | Wilczynski, Grzegorz M. Konopacki, Filip A. Wilczek, Ewa Lasiecka, Zofia Gorlewicz, Adam Michaluk, Piotr Wawrzyniak, Marcin Malinowska, Monika Okulski, Pawel Kolodziej, Lukasz R. Konopka, Witold Duniec, Kamila Mioduszewska, Barbara Nikolaev, Evgeni Walczak, Agnieszka Owczarek, Dorota Gorecki, Dariusz C. Zuschratter, Werner Ottersen, Ole Petter Kaczmarek, Leszek |
author_sort | Wilczynski, Grzegorz M. |
collection | PubMed |
description | Temporal lobe epilepsy (TLE) is a devastating disease in which aberrant synaptic plasticity plays a major role. We identify matrix metalloproteinase (MMP) 9 as a novel synaptic enzyme and a key pathogenic factor in two animal models of TLE: kainate-evoked epilepsy and pentylenetetrazole (PTZ) kindling–induced epilepsy. Notably, we show that the sensitivity to PTZ epileptogenesis is decreased in MMP-9 knockout mice but is increased in a novel line of transgenic rats overexpressing MMP-9. Immunoelectron microscopy reveals that MMP-9 associates with hippocampal dendritic spines bearing asymmetrical (excitatory) synapses, where both the MMP-9 protein levels and enzymatic activity become strongly increased upon seizures. Further, we find that MMP-9 deficiency diminishes seizure-evoked pruning of dendritic spines and decreases aberrant synaptogenesis after mossy fiber sprouting. The latter observation provides a possible mechanistic basis for the effect of MMP-9 on epileptogenesis. Our work suggests that a synaptic pool of MMP-9 is critical for the sequence of events that underlie the development of seizures in animal models of TLE. |
format | Text |
id | pubmed-2265409 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22654092008-09-10 Important role of matrix metalloproteinase 9 in epileptogenesis Wilczynski, Grzegorz M. Konopacki, Filip A. Wilczek, Ewa Lasiecka, Zofia Gorlewicz, Adam Michaluk, Piotr Wawrzyniak, Marcin Malinowska, Monika Okulski, Pawel Kolodziej, Lukasz R. Konopka, Witold Duniec, Kamila Mioduszewska, Barbara Nikolaev, Evgeni Walczak, Agnieszka Owczarek, Dorota Gorecki, Dariusz C. Zuschratter, Werner Ottersen, Ole Petter Kaczmarek, Leszek J Cell Biol Research Articles Temporal lobe epilepsy (TLE) is a devastating disease in which aberrant synaptic plasticity plays a major role. We identify matrix metalloproteinase (MMP) 9 as a novel synaptic enzyme and a key pathogenic factor in two animal models of TLE: kainate-evoked epilepsy and pentylenetetrazole (PTZ) kindling–induced epilepsy. Notably, we show that the sensitivity to PTZ epileptogenesis is decreased in MMP-9 knockout mice but is increased in a novel line of transgenic rats overexpressing MMP-9. Immunoelectron microscopy reveals that MMP-9 associates with hippocampal dendritic spines bearing asymmetrical (excitatory) synapses, where both the MMP-9 protein levels and enzymatic activity become strongly increased upon seizures. Further, we find that MMP-9 deficiency diminishes seizure-evoked pruning of dendritic spines and decreases aberrant synaptogenesis after mossy fiber sprouting. The latter observation provides a possible mechanistic basis for the effect of MMP-9 on epileptogenesis. Our work suggests that a synaptic pool of MMP-9 is critical for the sequence of events that underlie the development of seizures in animal models of TLE. The Rockefeller University Press 2008-03-10 /pmc/articles/PMC2265409/ /pubmed/18332222 http://dx.doi.org/10.1083/jcb.200708213 Text en Copyright © 2008, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Wilczynski, Grzegorz M. Konopacki, Filip A. Wilczek, Ewa Lasiecka, Zofia Gorlewicz, Adam Michaluk, Piotr Wawrzyniak, Marcin Malinowska, Monika Okulski, Pawel Kolodziej, Lukasz R. Konopka, Witold Duniec, Kamila Mioduszewska, Barbara Nikolaev, Evgeni Walczak, Agnieszka Owczarek, Dorota Gorecki, Dariusz C. Zuschratter, Werner Ottersen, Ole Petter Kaczmarek, Leszek Important role of matrix metalloproteinase 9 in epileptogenesis |
title | Important role of matrix metalloproteinase 9 in epileptogenesis |
title_full | Important role of matrix metalloproteinase 9 in epileptogenesis |
title_fullStr | Important role of matrix metalloproteinase 9 in epileptogenesis |
title_full_unstemmed | Important role of matrix metalloproteinase 9 in epileptogenesis |
title_short | Important role of matrix metalloproteinase 9 in epileptogenesis |
title_sort | important role of matrix metalloproteinase 9 in epileptogenesis |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265409/ https://www.ncbi.nlm.nih.gov/pubmed/18332222 http://dx.doi.org/10.1083/jcb.200708213 |
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