%0 Journal Article %T DP-b99 Modulates Matrix Metalloproteinase Activity and Neuronal Plasticity %A Marine Yeghiazaryan %A Izabela Rutkowska-Wlodarczyk %A Anna Konopka %A Grzegorz M. Wilczy¨˝ski %A Armenuhi Melikyan %A Eduard Korkotian %A Leszek Kaczmarek %A Izabela Figiel %J PLOS ONE %D 2014 %I Public Library of Science (PLoS) %R 10.1371/journal.pone.0099789 %X DP-b99 is a membrane-activated chelator of zinc and calcium ions, recently proposed as a therapeutic agent. Matrix metalloproteinases (MMPs) are zinc-dependent extracellularly operating proteases that might contribute to synaptic plasticity, learning and memory under physiological conditions. In excessive amounts these enzymes contribute to a number of neuronal pathologies ranging from the stroke to neurodegeneration and epileptogenesis. In the present study, we report that DP-b99 delays onset and severity of PTZ-induced seizures in mice, as well as displays neuroprotective effect on kainate excitotoxicity in hippocampal organotypic slices and furthermore blocks morphological reorganization of the dendritic spines evoked by a major neuronal MMP, MMP-9. Taken together, our findings suggest that DP-b99 may inhibit neuronal plasticity driven by MMPs, in particular MMP-9, and thus may be considered as a therapeutic agent under conditions of aberrant plasticity, such as those subserving epileptogenesis. %U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0099789