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The Journal of Neuroscience, February 1, 2002, 22(3):920-930
Matrix Metalloproteinase-9 Undergoes Expression and Activation during Dendritic Remodeling in Adult Hippocampus
Arek Szklarczyk1, 2, Joanna Lapinska1, Marcin Rylski1, 3, Ronald D. G. McKay2, and Leszek Kaczmarek1 1 Laboratory of Molecular Neurobiology, Nencki Institute, PL-02-093 Warsaw, Poland, 2 Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, and 3 Department of Genetics, Faculty of Biology, Warmia and Masuria University, PL-10-719 Olsztyn, Poland
Neurons of adult brain are able to remodel their synaptic connections in response to various stimuli. Modifications of the peridendritic environment, including the extracellular matrix, are likely to play a role during synapse remodeling. Proteolytic disassembly of ECM is a complex process using the regulated actions of specific extracellular proteinases. One of best-characterized families of matrix-modifying enzymes is the matrix metalloproteinase (MMP) family. Here, we describe changes in the expression and function of two well known MMPs, MMP-9 and MMP-2, in adult rat brain before and after systemic administration of the glutamate receptor agonist kainate. Kainate application results in enhanced synaptic transmission and seizures followed by selective tissue remodeling, primarily in hippocampal dentate gyrus. MMP-9 but not MMP-2 was highly expressed by neurons in normal adult rat brain. MMP-9 protein was localized in neuronal cell bodies and dendrites. Kainate upregulated the level of MMP-9 mRNA and protein within hours after drug administration. This was followed several hours later by MMP-9 enzymatic activation. Within hippocampus, MMP-9 mRNA and activity were increased selectively in dentate gyrus, including its dendritic layer. In addition, MMP-9 mRNA levels decreased in areas undergoing neuronal cell loss. This unique spatiotemporal pattern of MMP-9 expression suggests its involvement in activity-dependent remodeling of dendritic architecture with possible effects on synaptic physiology.
Key words: brain MMP-9 and MMP-2; matrix metalloproteinases; extracellular proteolysis; dendritic remodeling; hippocampus; mRNA translocation; brain extracellular matrix; kainic acid; neuronal activity-dependent gene expression
Copyright © 2002 Society for Neuroscience 0270-6474/02/223920-11$05.00/0
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