Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
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
_version_ 1782151474645565440
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
work_keys_str_mv AT wilczynskigrzegorzm importantroleofmatrixmetalloproteinase9inepileptogenesis
AT konopackifilipa importantroleofmatrixmetalloproteinase9inepileptogenesis
AT wilczekewa importantroleofmatrixmetalloproteinase9inepileptogenesis
AT lasieckazofia importantroleofmatrixmetalloproteinase9inepileptogenesis
AT gorlewiczadam importantroleofmatrixmetalloproteinase9inepileptogenesis
AT michalukpiotr importantroleofmatrixmetalloproteinase9inepileptogenesis
AT wawrzyniakmarcin importantroleofmatrixmetalloproteinase9inepileptogenesis
AT malinowskamonika importantroleofmatrixmetalloproteinase9inepileptogenesis
AT okulskipawel importantroleofmatrixmetalloproteinase9inepileptogenesis
AT kolodziejlukaszr importantroleofmatrixmetalloproteinase9inepileptogenesis
AT konopkawitold importantroleofmatrixmetalloproteinase9inepileptogenesis
AT dunieckamila importantroleofmatrixmetalloproteinase9inepileptogenesis
AT mioduszewskabarbara importantroleofmatrixmetalloproteinase9inepileptogenesis
AT nikolaevevgeni importantroleofmatrixmetalloproteinase9inepileptogenesis
AT walczakagnieszka importantroleofmatrixmetalloproteinase9inepileptogenesis
AT owczarekdorota importantroleofmatrixmetalloproteinase9inepileptogenesis
AT goreckidariuszc importantroleofmatrixmetalloproteinase9inepileptogenesis
AT zuschratterwerner importantroleofmatrixmetalloproteinase9inepileptogenesis
AT ottersenolepetter importantroleofmatrixmetalloproteinase9inepileptogenesis
AT kaczmarekleszek importantroleofmatrixmetalloproteinase9inepileptogenesis