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

Abstract

mice. Here, we investigated whether similar defects are also seen in dissociated and organotypic cultures from hippocampus and forebrain of tn-r 2/2 mice and whether the structure of PNs could be normalized.In tn-r 2/2 cultures, accumulations of several extracellular matrix molecules were mostly associated with somata, whereas dendrites were sparsely covered, compared with tn-r þ/þ mice. Experiments to normalize the structure of PNs in tn-r 2/2 organotypic slice cultures by depolarization of neurons, or by co-culturing tn-r þ/þ and tn-r 2/2 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.

Network‐based characterization of the synaptic proteome reveals that removal of epigenetic regulator Prmt8 restricts proteins associated with synaptic maturation

“…TNR is a crucial linker protein (Morawski et al . ; Mouw et al . ) in the mesh‐like structure known as perineuronal nets (PNNs; Fig.…”

Neural ECM and epilepsy

“…TN-R molecules assemble in dimers and trimmers, which can cross-link lecticans and by this way stabilize ECM, in particular in the dendritic compartment of aggrecan-rich perineuronal nets (Morawski et al, 2014). The perineuronal nets are composed of molecules that are synthesized by neurons and glial cells, such as hyaluronic acid, chondroitin sulfate proteoglycans (CSPGs) of the lectican family, link proteins, and tenascin-R (TN-R).…”

AMPA Receptor Antagonist NBQX Decreased Seizures by Normalization of Perineuronal Nets

“…Chondroitin sulfate proteoglycans (CSPGs) are crucial components of PNNs [20], which have been suggested to be a critical factor regulating synaptic plasticity [21]. Aberrant PNN signaling was found to induce the dysfunctions of central nervous system such as epilepsy, stroke, Alzheimer’s disease, schizophrenia and addiction [22,23]. The plant lectins Wisteria floribunda agglutinin ( WFA ) can be used to visualize PNNs by binding to N-acetylgalactosamine residue [24].…”