title: Important role of matrix metalloproteinase 9 in epileptogenesis.
abstract: 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.
authors.affiliation: Department of Neurophysiology, Nencki Institute, 02-093 Warsaw, Poland. G.Wilczynski@nencki.gov.pl
authors.forename: Grzegorz M
authors.initials: GM
authors.lastname: Wilczynski
authors.forename: Filip A
authors.initials: FA
authors.lastname: Konopacki
authors.forename: Ewa
authors.initials: E
authors.lastname: Wilczek
authors.forename: Zofia
authors.initials: Z
authors.lastname: Lasiecka
authors.forename: Adam
authors.initials: A
authors.lastname: Gorlewicz
authors.forename: Piotr
authors.initials: P
authors.lastname: Michaluk
authors.forename: Marcin
authors.initials: M
authors.lastname: Wawrzyniak
authors.forename: Monika
authors.initials: M
authors.lastname: Malinowska
authors.forename: Pawel
authors.initials: P
authors.lastname: Okulski
authors.forename: Lukasz R
authors.initials: LR
authors.lastname: Kolodziej
authors.forename: Witold
authors.initials: W
authors.lastname: Konopka
authors.forename: Kamila
authors.initials: K
authors.lastname: Duniec
authors.forename: Barbara
authors.initials: B
authors.lastname: Mioduszewska
authors.forename: Evgeni
authors.initials: E
authors.lastname: Nikolaev
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Walczak
authors.forename: Dorota
authors.initials: D
authors.lastname: Owczarek
authors.forename: Dariusz C
authors.initials: DC
authors.lastname: Gorecki
authors.forename: Werner
authors.initials: W
authors.lastname: Zuschratter
authors.forename: Ole Petter
authors.initials: OP
authors.lastname: Ottersen
authors.forename: Leszek
authors.initials: L
authors.lastname: Kaczmarek
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D003292:Convulsants; D049229:Dendritic Spines / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D006624:Hippocampus / Q000002:abnormalities* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D019599:Mossy Fibers, Hippocampal / Q000002:abnormalities / Q000473:pathology / Q000503:physiopathology; D009434:Neural Pathways / Q000002:abnormalities / Q000473:pathology / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000235:genetics; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000378:metabolism* / Q000473:pathology
chemical_list: D003292:Convulsants; D020780:Matrix Metalloproteinase 9