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.
相似文献