title: Tenascin-R promotes assembly of the extracellular matrix of perineuronal nets via clustering of aggrecan.
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.
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Morawski
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg - Eppendorf, Martinistr. 52, 20246 Hamburg, Germany Department of Neuroscience and Brain Technologies, Italian Institute of Technology, via Morego 30, Genoa, Italy Molecular Neuroplasticity Group, German Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Dityatev
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Hartlage-Rübsamen
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Blosa
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Holzer
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Flach
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany.
authors.forename: Sanja
authors.initials: S
authors.lastname: Pavlica
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg - Eppendorf, Martinistr. 52, 20246 Hamburg, Germany Department of Neuroscience and Brain Technologies, Italian Institute of Technology, via Morego 30, Genoa, Italy.
authors.forename: Galina
authors.initials: G
authors.lastname: Dityateva
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Grosche
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany.
authors.forename: Gert
authors.initials: G
authors.lastname: Brückner
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg - Eppendorf, Martinistr. 52, 20246 Hamburg, Germany Center for Neuroscience, Shantou University Medical College, 22 Xin Ling Road, Shantou 515041, People's Republic of China Keck Center for Collaborative Neuroscience and Department of Cell Biology, Rutgers University, 604 Allison Road, Piscataway, NJ 08554, USA schachner@stu.edu.cn.
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
mesh_terms: D053674:Aggrecans / Q000378:metabolism*; D000818:Animals; D018929:Cell Culture Techniques; D005109:Extracellular Matrix / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009836:Oligodendroglia / Q000502:physiology*; D019063:Tenascin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D053674:Aggrecans; D019063:Tenascin; C074638:tenascin R
keywords: aggregation; chondroitin sulfate proteoglycans; inhibitory interneurons; synaptic activity; synaptogenesis