Tenascin-R promotes assembly of the extracellular matrix of perineuronal nets via clustering of aggrecan.
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Tenascin-R promotes assembly of the extracellular matrix of perineuronal nets via clustering of aggrecan. / Morawski , Markus; Dityatev, Alexander; Hartlage-Rübsamen , Maike ; Blosa , Maren ; Holzer , Max ; Flach , Katharina ; Pavlica , Sanja ; Dityateva, Galina; Grosche, Jens ; Brückner , Gert ; Schachner, Melitta.
In: PHILOS T R SOC B, Vol. 369, No. 1654, 19.10.2014.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Tenascin-R promotes assembly of the extracellular matrix of perineuronal nets via clustering of aggrecan.
AU - Morawski , Markus
AU - Dityatev, Alexander
AU - Hartlage-Rübsamen , Maike
AU - Blosa , Maren
AU - Holzer , Max
AU - Flach , Katharina
AU - Pavlica , Sanja
AU - Dityateva, Galina
AU - Grosche, Jens
AU - Brückner , Gert
AU - Schachner, Melitta
PY - 2014/10/19
Y1 - 2014/10/19
N2 - 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.
AB - 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.
U2 - 10.1098/rstb.2014.0046
DO - 10.1098/rstb.2014.0046
M3 - SCORING: Journal article
VL - 369
JO - PHILOS T R SOC B
JF - PHILOS T R SOC B
SN - 0962-8436
IS - 1654
ER -