Matrix metalloproteinases (MMPs) are a growing family of zincdependent endopeptidases that are classically recognized as matrixremodeling enzymes implicated in various physiological and pathological processes. Apart from relatively well established detrimental role of MMPs, in particular gelatinases (MMP-2 and MMP-9), following brain injury, MMPs have been considered recently to be involved in the neurogenic response of the adult neural stem/progenitor cells after ischemic challenge. However, the role of these enzymes in the neurogenesis still remains to be clarified. The goal of the present study was to elucidate if activation of MMPs parallels the rate of neural progenitor cells proliferation and/or further differentiation. Our results show that post-ischemic acceleration in the proliferation and differentiation of progenitors in the dentate gyrus of the adult hippocampus coincides with the remarkable elevation of MMPs activity. On the contrary, in the ischemia-damaged CA1 pyramidal cells layer the activity of MMPs fell below the control level. It should be pointed out, that in this structure neurogenesis seems to be rather elusive, as we did not found evidence for production of a new matured neurons. In an effort to further check the potential participation of MMPs in neurogenesis-associated processes we have tested the effect of MMPs inhibitors (GM6001 and doxycycline) on neural stem cells line. We observed that the addition of these agents decreased the rate of proliferation and differentiation toward neurons. In conclusion, the spatial and temporal profile of MMPs activity during reperfusion following transient forebrain ischemia suggest that these proteinases might belong to the discussed mechanism(s) which govern neurogenesis-associated processes in ischemic brain hippocampus. Supported by MSHE grant no 0154/B/P01/2009/38.
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