The role of matrix metalloproteinase mmp-9 in peripheral neural system regeneration

Multiple lines of evidence show that matrix metalloproteinases (MMPs) are involved in the peripheral neural system degenerative and regenerative processes. MMP-9 was suggested in particular to play a role in the peripheral nerve after injury or during Wallerian degeneration. Interestingly, our previous analysis of Lpin1 mutant mice (which present morphological signs of active demyelination and acute inflammatory cell migration, similar to processes present in the PNS undergoing Wallerian degeneration) revealed an accumulation of MMP-9 in the endoneurium of affected animals. We therefore generated a mouse line lacking both the Lpin1 and the MMP-9 genes in order to determine if MMP-9 plays a role in either inhibition or potentiation of the demyelinating phenotype present in Lpin1 knockout mice. The inactivation of MMP-9 alone did not lead to defects in PNS structure or function. Interestingly we observed that the double mutant animals showed reduced nerve conduction velocity, lower myelin protein mRNA expressions, and had more histological abnormalities as compared to the Lpin1 single mutants. In addition, based on immunohistochemical analysis and macrophage markers mRNA expression, we found a lower macrophage content in the sciatic nerve of the double mutant animals. Together our data indicate that MMP-9 plays a role in macrophage recruitment during postinjury PNS regeneration processes and suggest that slower macrophage infiltration delays regenerative processes in PNS