@article{ref1,
title="MT5-MMP, ADAM-10 and N-cadherin Act in Concert to Facilitate Synapse Reorganization Following Traumatic Brain Injury",
journal="Journal of neurotrauma",
year="2012",
author="Warren, Kelly and Reeves, Thomas and Phillips, Linda",
volume="29",
number="10",
pages="1922-1940",
abstract="Matrix metalloproteinases (MMPs) influence synaptic recovery following traumatic brain injury (TBI). Membrane type 5-metalloproteinase (MT5-MMP) and a distintegrin and metalloproteinase -10 (ADAM-10) are membrane-bound MMPs which cleave N-cadherin, a protein critical to synapse stabilization. This study examined protein and mRNA expression of MT5-MMP, ADAM-10 and N-cadherin after TBI, contrasting adaptive and maladaptive synaptogenesis. The effect of MMP inhibition on MT5-MMP, ADAM-10 and N-cadherin was assessed during maladaptive plasticity and correlated with synaptic function. Rats were subjected to adaptive unilateral entorhinal cortical lesion (UEC) or maladaptive fluid percussion TBI + bilateral entorhinal cortical lesion (TBI+BEC). Hippocampal MT5-MMP and ADAM-10 protein was significantly elevated 2 and 7d postinjury. At 15d after UEC, each MMP returned to control level, while TBI+BEC ADAM-10 remained elevated. At 2 and 7d, N-cadherin protein was below control. By the 15d synapse stabilization phase, UEC N-cadherin rose above control, a shift not seen for TBI+BEC. At 7d, increased TBI+BEC ADAM-10 transcript correlated with protein elevation. UEC ADAM-10 mRNA did not change, and no differences in MT5-MMP or N-cadherin mRNA were detected. Confocal imaging showed MT5-MMP, ADAM-10 and N-cadherin localization within reactive astrocytes. MMP inhibition attenuated ADAM-10 protein 15d after TBI+BEC and increased N-cadherin. This inhibition partially restored long-term potentiation induction, but did not affect paired-pulse facilitation. Results confirm time and injury dependent expression of MT5-MMP, ADAM-10 and N-cadherin during reactive synaptogenesis. Persistent ADAM-10 expression was correlated with attenuated N-cadherin level and reduced functional recovery. MMP inhibition shifted ADAM-10 and N-cadherin toward adaptive expression and improved synaptic function.<p /> <p>Language: en</p>",
language="en",
issn="0897-7151",
doi="10.1089/neu.2012.2383",
url="http://dx.doi.org/10.1089/neu.2012.2383"
}