Journal article
Inhibition of Hippocampal Matrix Metalloproteinase-3 and -9 Disrupts Spatial Memory
Neural plasticity, Vol.2007, pp.73813-8
2007
Handle:
https://hdl.handle.net/2376/110092
PMCID: PMC1838960
PMID: 17502908
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
μ
M, 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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Details
- Title
- Inhibition of Hippocampal Matrix Metalloproteinase-3 and -9 Disrupts Spatial Memory
- Creators
- John W Wright - Department of Psychology, Washington State University, Pullman, WA 99164-4820, USATravis E Brown - Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA 99164-6520, USAJoseph W Harding - Department of Psychology, Washington State University, Pullman, WA 99164-4820, USA
- Publication Details
- Neural plasticity, Vol.2007, pp.73813-8
- Academic Unit
- Psychology, Department of; Integrative Physiology and Neuroscience, Department of
- Publisher
- Hindawi Publishing Corporation
- Identifiers
- 99900547702801842
- Language
- English
- Resource Type
- Journal article