| First Author | Wilczynski GM | Year | 2008 |
| Journal | J Cell Biol | Volume | 180 |
| Issue | 5 | Pages | 1021-35 |
| PubMed ID | 18332222 | Mgi Jnum | J:136000 |
| Mgi Id | MGI:3794925 | Doi | 10.1083/jcb.200708213 |
| Citation | Wilczynski GM, et al. (2008) Important role of matrix metalloproteinase 9 in epileptogenesis. J Cell Biol 180(5):1021-35 |
| abstractText | Temporal lobe epilepsy (TLE) is a devastating disease in which aberrant synaptic plasticity plays a major role. We identify matrix metalloproteinase (MMP) 9 as a novel synaptic enzyme and a key pathogenic factor in two animal models of TLE: kainate-evoked epilepsy and pentylenetetrazole (PTZ) kindling-induced epilepsy. Notably, we show that the sensitivity to PTZ epileptogenesis is decreased in MMP-9 knockout mice but is increased in a novel line of transgenic rats overexpressing MMP-9. Immunoelectron microscopy reveals that MMP-9 associates with hippocampal dendritic spines bearing asymmetrical (excitatory) synapses, where both the MMP-9 protein levels and enzymatic activity become strongly increased upon seizures. Further, we find that MMP-9 deficiency diminishes seizure-evoked pruning of dendritic spines and decreases aberrant synaptogenesis after mossy fiber sprouting. The latter observation provides a possible mechanistic basis for the effect of MMP-9 on epileptogenesis. Our work suggests that a synaptic pool of MMP-9 is critical for the sequence of events that underlie the development of seizures in animal models of TLE. |
