Matrix metalloproteinase-9 activity increased by two different types of epileptic seizures that do not induce neuronal death: A possible role in homeostatic synaptic plasticity

Eszter Takács, Rita Nyilas, Zsuzsanna Szepesi, Péter Baracskay, Bente Karlsen, Tina Røsvold, Alvhild A. Bjørkum, András Czurkó, Zsolt Kovács, Adrienna K. Kékesi, Gábor Juhász

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Matrix metalloproteases (MMPs) degrade or modify extracellular matrix or membrane-bound proteins in the brain. MMP-2 and MMP-9 are activated by treatments that result in a sustained neuronal depolarization and are thought to contribute to neuronal death and structural remodeling. At the synapse, MMP actions on extracellular proteins contribute to changes in synaptic efficacy during learning paradigms. They are also activated during epileptic seizures, and MMP-9 has been associated with the establishment of aberrant synaptic connections after neuronal death induced by kainate treatment. It remains unclear whether MMPs are activated by epileptic activities that do not induce cell death. Here we examine this point in two animal models of epilepsy that do not involve extensive cell damage. We detected an elevation of MMP-9 enzymatic activity in cortical regions of secondary generalization after focal seizures induced by 4-aminopyridine (4-AP) application in rats. Pro-MMP-9 levels were also higher in Wistar Glaxo Rijswijk (WAG/Rij) rats, a genetic model of generalized absence epilepsy, than they were in Sprague-Dawley rats, and this elevation was correlated with diurnally occurring spike-wave-discharges in WAG/Rij rats. The increased enzymatic activity of MMP-9 in these two different epilepsy models is associated with synchronized neuronal activity that does not induce widespread cell death. In these epilepsy models MMP-9 induction may therefore be associated with functions such as homeostatic synaptic plasticity rather than neuronal death.

Original languageEnglish
Pages (from-to)799-809
Number of pages11
JournalNeurochemistry international
Issue number6-7
Publication statusPublished - May 1 2010



  • 4-AP
  • Gelatinases
  • MMP-2
  • MMP-9
  • Seizures
  • WAG/Rij rats

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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