Kwok, J.
John van Geest Centre for Brain Repair, University of Cambridge, United Kingdom
Chondroitin sulphate proteoglycans (CSPGs) has been widely reported in the central nervous system (CNS) and their up-regulation in the glial scar after injury is a strong deterrent to regeneration. Removal of CSPGs in the lesion area successfully restores functional recovery. Recently, CSPGs are also reported in a highly aggregated structure called perineronal nets (PNNs) which are important to plasticity in the brain. PNNs wrap around the neuronal surface and are found circumferencing synapses. To understand the molecular assembly of the aggregates and their corresponding contributions to the PNNs, we created an in vitro model for the PNNs. While hyaluronan, link proteins, tenascin R and aggrecan (a CSPG) are the key components for the assembly of the PNNs, the sulphation modification(s) on the CSPGs is important in controlling the binding of functional effectors to the PNNs. With the use of link protein knockout mice, we subsequently observed that the mice retain juvenile plasticity in the visual cortex till adulthood. We also demonstrated that one of the PNN effectors semaphorin 3A binds specifically to chondroitin sulphate E (CS-E) with C-4,6-sulphations. Blocking CS-E epitopes using anti-CS-E antibodies partially neutralises this binding and renders the PNNs less inhibitory in vitro. These results suggest that manipulation of PNNs by their assembly or sulphation may be useful in enhancing plasticity after injury in the CNS.