期刊
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
卷 369, 期 1654, 页码 -出版社
ROYAL SOC
DOI: 10.1098/rstb.2014.0046
关键词
aggregation; chondroitin sulfate proteoglycans; inhibitory interneurons; synaptogenesis; synaptic activity
类别
资金
- Deutsche Forschungsgemeinschaft [BR 1208/3-3, 4, SCHA 185/29-3,4, MO 2249/2-1, PP 1608]
- COST Action 'Brain Extracellular Matrix in Health and Disease' from the European Commission [BM1001]
- Alzheimer Forschungsinitiative e.V. (AFI) [11861]
- European Union
- Free State of Saxony [SAB 100154907]
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.
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