Tenascin-R promotes assembly of the extracellular matrix of perineuronal nets via clustering of aggrecan

Markus Morawski, Alexander Dityatev, Maike Hartlage-Rübsamen, Maren Blosa, Max Holzer, Katharina Flach, Sanja Pavlica, Galina Dityateva, Jens Grosche, Gert Brückner, Melitta Schachner

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57 Scopus citations

Abstract

Perineuronal nets (PNs) in the brains of tenascin-R-deficient (tn-r-/-) mice develop in temporal concordance with those of wild-type (tn-r+/+) mice. However, the histological appearance of PNs is abnormal in adult tn-r-/- mice. Here, we investigated whether similar defects are also seen in dissociated and organotypic cultures from hippocampus and forebrain of tn-r-/- mice and whether the structure of PNs could be normalized. In tn-r-/- cultures, accumulations of several extracellular matrix molecules were mostly associated with somata, whereas dendrites were sparsely covered, compared with tn-r+/+ mice. Experiments to normalize the structure of PNs in tn-r-/- organotypic slice cultures by depolarization of neurons, or by co-culturing tn-r+/+ and tn-r-/- brain slices failed to restore a normal PN phenotype. However, formation of dendritic PNs in cultures was improved by the application of tenascin-R protein and rescued by polyclonal antibodies to aggrecan and a bivalent, but not monovalent form of the lectin Wisteria floribunda agglutinin. These results show that tenascin-R and aggrecan are decisive contributors to formation and stabilization of PNs and that tenascin-R may implement these functions by clustering of aggrecan. Proposed approaches for restoration of normal PN structure are noteworthy in the context of PN abnormalities in neurological disorders, such as epilepsy, schizophrenia and addiction.

Original languageEnglish (US)
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Volume369
Issue number1654
DOIs
StatePublished - Oct 19 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Keywords

  • Aggregation
  • Chondroitin sulfate proteoglycans
  • Inhibitory interneurons
  • Synaptic
  • Synaptogenesis

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