Cited by 71Memory and Neural MechanismsProtease and Inhibitor MechanismsNeurogenesis and neuroplasticity mechanisms

Inhibition of hippocampal matrix metalloproteinase-3 and -9 disrupts spatial memory

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Wright, John W., Brown, Travis E., Harding, Joseph W.·2007·Neural Plasticity

Abstract

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 muM, 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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Authors
Wright, J. W., Brown, T. E., & Harding, J. W.
Affiliations
Washington State University (US)
Corresponding author
Wright, John W.
Venue
Neural Plasticity
Publisher
Wiley
Published
2007
Volume
2007
Pages
1-8
ISSN
  • 1687-5443 (ISSN-L)
  • 2090-5904
OpenAlex
W2107137914
Cited by
71
References
42
Citations by year
2026: 1 · 2024: 6 · 2023: 3 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 4 · 2014: 1 · 2013: 5 · 2012: 4
FWCI
3.00
Type
journal article
Language
en
Open access
Locations
  • Neural Plasticity (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Science Foundation (IBN-0091337)
  • Pacific Northwest Biotechnology (IBN-0091337)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
matrix metalloproteinase-3, MMP-9, hippocampus, spatial memory, memory consolidation, extracellular matrix, matrix metalloproteinase inhibitors, dorsal hippocampus, prefrontal cortex, Morris water maze, gelatinase activity
MeSH terms
Animals, Enzyme Inhibitors, Hippocampus, Male, Memory, Spatial Behavior, Rats, Sprague-Dawley, Maze Learning, Matrix Metalloproteinase 3, Matrix Metalloproteinase 9, Rats, Matrix Metalloproteinase Inhibitors

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