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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...

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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
Descripción
Sumario: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.