Inhibition of hippocampal matrix metalloproteinase-3 and -9 disrupts spatial memory
Open accessAbstract
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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Disrupting MMP3 and MMP9 activity in hippocampus impairs spatial memory and avoidance learning.
“Similar disruption of MMP3 and MMP9 activity in the hippocampus results in disruption of spatial memory and avoidance learning (Nagy et al., 2007; Wright et al., 2007).”
From Losing the sugar coating: Potential impact of perineuronal net abnormalities on interneurons in schizophrenia (2015) · cites this paper as Wright et al., 2007
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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
- PMC
- PMC1838960
- 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
- gold
- doi.org
- 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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