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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.

SUBMITTER: Morawski M 

PROVIDER: S-EPMC4173296 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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

Morawski Markus M   Dityatev Alexander A   Hartlage-Rübsamen Maike M   Blosa Maren M   Holzer Max M   Flach Katharina K   Pavlica Sanja S   Dityateva Galina G   Grosche Jens J   Brückner Gert G   Schachner Melitta M  

Philosophical transactions of the Royal Society of London. Series B, Biological sciences 20141001 1654


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 m  ...[more]

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