Abstract
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.
Original language | English |
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Article number | e99789 |
Pages (from-to) | 1-9 |
Number of pages | 9 |
Journal | PLoS ONE |
Volume | 9 |
Issue number | 6 |
DOIs | |
Publication status | Published - 11 Jun 2014 |
Externally published | Yes |
Keywords
- Animals
- Chelating Agents
- Dendritic Spines
- Egtazic Acid
- Hippocampus
- Kainic Acid
- Male
- Matrix Metalloproteinase 9
- Mice
- Mice, Inbred C57BL
- Neuronal Plasticity
- Seizures
- Journal Article
- Research Support, Non-U.S. Gov't