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Inhibition of Hippocampal Matrix Metalloproteinase-3 and -9 Disrupts Spatial Memory

Memory consolidation requires synaptic reconfiguration dependent upon extracellular matrix (ECM) molecules interacting with cell adhesion molecules. Matrix metalloproteinase (MMP) activity is responsible for transient alterations in the ECM that may be prerequisite to hippocampal-dependent learning....

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Detalles Bibliográficos
Autores principales: Wright, John W., Brown, Travis E., Harding, Joseph W.
Formato: Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1838960/
https://www.ncbi.nlm.nih.gov/pubmed/17502908
http://dx.doi.org/10.1155/2007/73813
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author Wright, John W.
Brown, Travis E.
Harding, Joseph W.
author_facet Wright, John W.
Brown, Travis E.
Harding, Joseph W.
author_sort Wright, John W.
collection PubMed
description Memory consolidation requires synaptic reconfiguration dependent upon extracellular matrix (ECM) molecules interacting with cell adhesion molecules. Matrix metalloproteinase (MMP) activity is responsible for transient alterations in the ECM that may be prerequisite to hippocampal-dependent learning. In support of this hypothesis we have measured increases in MMP-3 and MMP-9 levels within the hippocampus and prefrontal cortex during Morris water maze training. The present investigation extends these findings by determining that infusion of an MMP inhibitor (FN-439) into the dorsal hippocampus disrupted acquisition of this task. In vitro fluorescence enzyme assays to determine the specificity of FN-439 against the catalytic domains of MMP-3 and MMP-9 indicated mean ± SEM IC(50)s of 16.2 ± 7.8 and 210.5 ± 37.8 μM, respectively, while in situ zymography using hippocampal sections treated with FN-439 indicated significant reductions in MMP gelatinase activity. These results suggest that compromising the ability of the dorsal hippocampus to reconfigure ECM molecules by inhibiting MMP activity interferes with appropriate spatial memory acquisition, and support a role for hippocampal MMPs in the phenomena of spatial memory acquisition and storage.
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spelling pubmed-18389602007-05-14 Inhibition of Hippocampal Matrix Metalloproteinase-3 and -9 Disrupts Spatial Memory Wright, John W. Brown, Travis E. Harding, Joseph W. Neural Plast Research Article Memory consolidation requires synaptic reconfiguration dependent upon extracellular matrix (ECM) molecules interacting with cell adhesion molecules. Matrix metalloproteinase (MMP) activity is responsible for transient alterations in the ECM that may be prerequisite to hippocampal-dependent learning. In support of this hypothesis we have measured increases in MMP-3 and MMP-9 levels within the hippocampus and prefrontal cortex during Morris water maze training. The present investigation extends these findings by determining that infusion of an MMP inhibitor (FN-439) into the dorsal hippocampus disrupted acquisition of this task. In vitro fluorescence enzyme assays to determine the specificity of FN-439 against the catalytic domains of MMP-3 and MMP-9 indicated mean ± SEM IC(50)s of 16.2 ± 7.8 and 210.5 ± 37.8 μM, respectively, while in situ zymography using hippocampal sections treated with FN-439 indicated significant reductions in MMP gelatinase activity. These results suggest that compromising the ability of the dorsal hippocampus to reconfigure ECM molecules by inhibiting MMP activity interferes with appropriate spatial memory acquisition, and support a role for hippocampal MMPs in the phenomena of spatial memory acquisition and storage. Hindawi Publishing Corporation 2007 2006-12-14 /pmc/articles/PMC1838960/ /pubmed/17502908 http://dx.doi.org/10.1155/2007/73813 Text en Copyright © 2007 John W. Wright et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wright, John W.
Brown, Travis E.
Harding, Joseph W.
Inhibition of Hippocampal Matrix Metalloproteinase-3 and -9 Disrupts Spatial Memory
title Inhibition of Hippocampal Matrix Metalloproteinase-3 and -9 Disrupts Spatial Memory
title_full Inhibition of Hippocampal Matrix Metalloproteinase-3 and -9 Disrupts Spatial Memory
title_fullStr Inhibition of Hippocampal Matrix Metalloproteinase-3 and -9 Disrupts Spatial Memory
title_full_unstemmed Inhibition of Hippocampal Matrix Metalloproteinase-3 and -9 Disrupts Spatial Memory
title_short Inhibition of Hippocampal Matrix Metalloproteinase-3 and -9 Disrupts Spatial Memory
title_sort inhibition of hippocampal matrix metalloproteinase-3 and -9 disrupts spatial memory
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1838960/
https://www.ncbi.nlm.nih.gov/pubmed/17502908
http://dx.doi.org/10.1155/2007/73813
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