MMP-2: A modulator of neuronal precursor activity and cognitive and motor behaviors.

Matrix Metalloproteinase2, (MMP2, gelatinase A) is a zinc-containing enzyme with a broad substrate specificity including components of the extracellular matrix, cell surface molecules and a wide range bioactive molecules. MMP2 is known to play important roles in a variety of signaling pathways and processes in a wide range of cell types and tissues. In this report we elucidate the effects of the absence of MMP2 in Neural Precursor Cells (NPC) derived from C57BL/6 MMP2 KO mice and in primary and secondary neurosphere formation. We observed smaller neurosphere numbers and sizes, decreased NPC numbers, PCNA expression, DNA and Akt activation in MMP2 KO NPC compared to WT NPC. We also found decreased neurosphere formation and NPC migration outward from adherent neurospheres, decreased CXCR4 and nestin expression and increased GFAP and neuro-filament expression in MMP2 KO NPC compared to Wt NPC. MMP2 KO mice were found to exhibit increased anxiety manifested in open field activity assays compared to Wt mice. MMP2 KO mice also exhibited differences in motor activities manifested by decreased balance and endurance during Rota-rod testing. These studies illustrate an important role of MMP2 in cognitive and motor behaviors and confirm its importance in NPC activities crucial to brain development, growth and response to and recovery from injury.