Important role of matrix metalloproteinase 9 in epileptogenesis
Open accessAbstract
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.
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Metalloproteinase inhibitors prevented seizures and MMP-9 knockout mice were less susceptible to pentylenetetrazole-induced seizures.
“Moreover, metalloproteinase inhibitors prevented seizures51 and MMP-9 knockout mice were less susceptible to pentylenetetrazole-induced seizures52.”
From Perineuronal nets decrease membrane capacitance of peritumoral fast spiking interneurons in a model of epilepsy (2018) · cites this paper as [52]
MMP activity co-localizes with excitatory synapses.
“Consistent with previous studies in the hippocampus (Wilczynski et al., 2008; Bozdagi et al., 2007; Gawlak et al., 2009), we demonstrated that MMP activity co-localizes with excitatory synapses.”
From Light reintroduction after dark exposure reactivates plasticity in adults via perisynaptic activation of MMP-9 (2017) · cites this paper as Wilczynski et al., 2008
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- Authors
- Wilczynski, G. M., Konopacki, F. A., Wilczek, E., Lasiecka, Z., Gorlewicz, A., Michaluk, P., Wawrzyniak, M., Malinowska, M., Okulski, P., Kolodziej, L. R., Konopka, W., Duniec, K., Mioduszewska, B., Nikolaev, E., Walczak, A., Owczarek, D., Gorecki, D. C., Zuschratter, W., Ottersen, O. P., & Kaczmarek, L.
- Affiliations
- Instytut Biologii Doświadczalnej im. Marcelego Nenckiego (PL)
- Medical University of Warsaw (PL)
- 1Department of Neurophysiology and
- 6Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, PO1 2DT Portsmouth, England, UK
- Leibniz Institute for Neurobiology (DE)
- University of Oslo (NO)
- ORCID
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2008-03-10
- Volume
- 180
- Issue
- 5
- Pages
- 1021-1035
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2265409
- OpenAlex
- W2102444756
- Cited by
- 292
- References
- 57
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 13 · 2023: 19 · 2022: 11 · 2021: 15 · 2020: 15 · 2019: 18 · 2018: 21 · 2017: 13 · 2016: 17 · 2015: 19 · 2014: 22 · 2013: 23 · 2012: 22
- FWCI
- 11.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- MMP-9, epileptogenesis, temporal lobe epilepsy, synaptic plasticity, dendritic spines, mossy fiber sprouting, synaptogenesis, kainate-induced epilepsy, pentylenetetrazole kindling, MMP-9 knockout mice, hippocampus, seizures
- MeSH terms
- Animals, Convulsants, Disease Models, Animal, Epilepsy, Hippocampus, Male, Mice, Inbred C57BL, Neural Pathways, Neuronal Plasticity, Organ Culture Techniques, Synapses, Microscopy, Immunoelectron, Rats, Wistar, Mice, Knockout, Mossy Fibers, Hippocampal, Matrix Metalloproteinase 9, Animals, Genetically Modified, Dendritic Spines, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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