Retarded kindling progression in mice deficient in the extracellular matrix glycoprotein tenascin-R.

We investigated the role of the extracellular matrix glycoprotein tenascin-R (TNR) in formation of a hyperexcitable network in the kindling model of epilepsy. The idea that TNR may be important for this process was suggested by previous studies showing that deficiency in TNR leads to abnormalities in synaptic plasticity, perisomatic GABAergic inhibition and more astrocytes in the hippocampus of adult mice.
Constitutively TNR deficient (TNR-/-) mice and their wild-type littermates received repeated electrical stimulation in the amygdala over several days until they developed fully kindled generalized seizures at which time their brains were studied immunohistochemically.
In TNR-/- mice, kindling progression was retarded compared with wild-type littermate controls. Morphological analysis of the mice used for the kindling studies revealed that, independently of genotype, numbers of parvalbumin-positive interneurons in the dentate gyrus correlated positively with afterdischarge threshold alterations in kindled mice. The kindling-induced increase in the number of S100 expressing astrocytes in the dentate gyrus was enhanced by TNR deficiency and correlated negatively with the kindling rate.
Our data support the view that TNR promotes formation of a hyperexcitable network during kindling and suggest that an increase in S100-expressing astrocytes may contribute to retarded epileptogenesis in TNR-/- mice.
AuthorsKatrin Hoffmann, Elena Sivukhina, Heidrun Potschka, Melitta Schachner, Wolfgang Löscher, Alexander Dityatev
JournalEpilepsia (Epilepsia) Vol. 50 Issue 4 Pg. 859-69 (Apr 2009) ISSN: 1528-1167 [Electronic] United States
PMID19178559 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Parvalbumins
  • Sterol Regulatory Element Binding Protein 1
  • Tenascin
  • tenascin R
  • Amygdala (physiopathology)
  • Analysis of Variance
  • Animals
  • Astrocytes (metabolism)
  • Cell Count (methods)
  • Disease Models, Animal
  • Electric Stimulation (adverse effects)
  • Epilepsy (genetics, pathology, physiopathology)
  • Gene Expression Regulation (genetics)
  • Hippocampus (pathology)
  • Interneurons (metabolism)
  • Kindling, Neurologic (genetics)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Parvalbumins (metabolism)
  • Statistics, Nonparametric
  • Sterol Regulatory Element Binding Protein 1 (metabolism)
  • Tenascin (deficiency)

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