Spatiotemporal expression patterns of metalloproteinases and their inhibitors in the postnatal developing rat cerebellum

Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade the c omponents of the extracellular matrix (ECM). The balance between MMPs and t heir inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] in the pe ricellular environment determines the most significant proteolytic events i n tissue remodeling. In vitro evidence is accumulating that these molecules may be crucial in the maturation of neural cells. Here, we investigated th e in vivo expression of MMPs 2, 3, and 9 and TIMPs 1, 2, and 3 in the devel oping and adult rat cerebellum using immunohistochemistry and in situ hybri dization. During postnatal development, all Purkinje (PK) cell somata expre ssed all the MMPs and TIMPs studied, whereas their growing dendritic trees expressed only MMP 3 and TIMP 3. In the adult, MMP 3 was confined to PK cel l bodies, whereas TIMP 3 was expressed in PK cell somata and processes. Irr espective of the developmental stage, Bergmann glial processes contained on ly MMP 9, but their somata contained both TIMP 1 and MMP 9. In granular cel ls, MMPs 3 and 9 and TIMPs 1, 2, and 3 were chiefly detected at a time when migration is known to be maximal; except for that of TIMP 1, their express ion persisted in the internal granular layer in the adult. The functional r elevance of MMP expression was verified by gelatin zymography. MMP 9 activi ty was maximal on postnatal day 10 (P10) and was detectable at a low level on P15 and in the adult, whereas MMP 2 activity remained similar throughout postnatal development. Regional and cell-specific expression of MMPs and T IMPs closely reflects the successive stages of cerebellar development, ther eby suggesting a pivotal role for ECM proteolysis in brain development and plasticity.