Matrix metalloproteinase-9-a culprit in epilepsy?

• Autorzy: Wilczynski G.M.
• Języki publikacji: EN

Abstrakty

EN

Temporal lobe epilepsy (TLE) is a chronic devastating disease in which aberrant synaptic plasticity plays a major role. Recently, MMP-9, a matrix metalloproteinase, has been implicated synaptic plasticity, long-term potentiation and learning and memory formation. Therefore, MMP-9 might play a pathogenic role in epileptogenesis. Indeed, the recent study revealed MMP-9 as a novel synaptic enzyme, and a key pathogenic factor in two distinct animal models of TLE: kainate-evoked-epilepsy and pentylenetetrazole (PTZ) kindling-induced epilepsy. In particular, sensitivity to PTZ-induced epileptogenesis is decreased in MMP-9 knockout (KO) mice, whereas it is increased in MMP-9-overexpressing rats. Moreover, confocal- and immunoelectron-microscopic analyses demonstrated that MMP-9 associates with hippocampal dendritic spines bearing asymmetric (excitatory) synapses. In addition, both MMP-9 protein levels as well as its enzymatic activity become strongly increased upon seizures. Furthermore, MMP-9-defi ciency diminishes seizure-evoked pruning of dendritic spines and, most importantly (with regards to epileptogenesis), it decreases aberrant synapse formation following mossyfi bers sprouting. Taken together, the aforementioned results suggest that the synaptic pool of MMP-9 is critically involved in the sequence of events that underlie epileptogenesis in two commonly used models of TLE.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 1
• Opis fizyczny: p.93-94

Twórcy

autor

Wilczynski G.M.

• Laboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland