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Seizure activity in dogs is associated with enhanced TIMP-2 expression of microglia

Veronika M Stein1, Sem Genini, Christina Puff

  • 1Department of Small Animal Medicine and Surgery, University of Veterinary Medicine, Bünteweg 9, 30559 Hannover, Germany. veronika.stein@tiho-hannover.de

Veterinary Immunology and Immunopathology
|March 3, 2012
PubMed

Insights

Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) influence brain plasticity and epilepsy. In dogs with seizures, microglial TIMP-2 expression was significantly upregulated, suggesting a role in seizure generation.

Area of Science:

  • Neuroscience
  • Pathology
  • Molecular Biology

Background:

  • Aberrant synaptic plasticity is key in epilepsy pathogenesis.
  • Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate central nervous system (CNS) remodeling and synaptic plasticity.
  • MMPs and TIMPs may play a crucial role in epileptogenesis.

Purpose of the Study:

  • To investigate the pathogenetic role of microglial MMPs and TIMPs in seizure induction.
  • To examine the expression profiles of specific MMPs, TIMPs, and RECK in microglial cells from dogs with and without seizures.

Main Methods:

  • Comparative examination of 24 dogs with various intracranial diseases, with and without seizures.
  • Isolation of microglial cells using density gradient centrifugation.
  • Quantitative real-time PCR (qPCR) to analyze the expression of MMP-2, MMP-9, MMP-12, MMP-13, MMP-14, TIMP-1, TIMP-2, and RECK.

Main Results:

  • A significant upregulation of TIMP-2 expression was observed in dogs suffering from seizures.
  • This is the first reported instance of TIMP-2 upregulation in seizure-affected dogs.

Conclusions:

  • Microglial TIMP expression, particularly TIMP-2, may be implicated in the generation of seizures.
  • Further research into microglial TIMP involvement in epileptogenesis is warranted.

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