期刊
JOURNAL OF NEUROSCIENCE RESEARCH
卷 84, 期 4, 页码 768-781出版社
WILEY
DOI: 10.1002/jnr.20986
关键词
matrix metalloproteinase; synaptogenesis; hippocampus; neurotrauma
资金
- NINDS NIH HHS [NS-44372, R01 NS044372] Funding Source: Medline
- PHS HHS [NSO-07288] Funding Source: Medline
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS044372, R56NS044372] Funding Source: NIH RePORTER
The interaction between extracellular matrix (ECM) and regulatory matrix metalloproteinases (MMPs) is important in establishing and maintaining synaptic connectivity. By using fluid percussion traumatic brain injury (TBI) and combined TBI and bilateral entorhinal cortical lesion (TBI + BEC), we previously demonstrated that hippocampal stromelysin-1 (MMP-3) expression and activity increased during synaptic plasticity. We now report a temporal analysis of MMP-3 protein and mRNA response to TBI during both degenerative (2 day) and regenerative (7, 15 day) phases of reactive synaptogenesis. MMP-3 expression during successful synaptic reorganization (following unilateral entorhinal cortical lesion; UEC) was compared with MMP-3 expression when normal synaptogenesis fails (after combined TBI + BEC insult). Increased expression of MMP-3 protein and message was observed in both models at 2 days postinjury, and immuohistochemical (IHC) colocalization suggested that reactive astrocytes contribute to that increase. By 7 days postinjury, model differences in MMP-3 were observed. UEC MMP-3 mRNA was equivalent to control, and MMP-3 protein was reduced within the deafferented region. In contrast, enzyme mRNA remained elevated in the maladaptive TBI + BEC model, accompanied by persistent cellular labeling of MMP-3 protein. At 15 days survival, MMP-3 mRNA was normalized in each model, but enzyme protein remained higher than paired controls. When TBI + BEC recovery was enhanced by the N-methyl-D-aspartate antagonist MK-801, 7-day MMP-3 mRNA was significantly reduced. Similarly, MMP inhibition with FN-439 reduced the persistent spatial learning deficits associated with TBI + BEC insult. These results suggest that MMP-3 might differentially affect the sequential phases of reactive synaptogenesis and exhibit an altered pattern when recovery is perturbed. (c) 2006 Wiley-Liss, Inc.
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