Repulsion of cerebellar granule neurons by chondroitin sulfate proteoglycans is mediated by MAPK pathway

Inhibitory molecules associated with myelin and glial scar formation inhibit axon regeneration after an injury to the central nervous system (CNS). Chondroitin sulfate proteoglycans (CSPGs) that are expressed in the scar contribute to the non-permissive properties of the CNS environment. Here, we employed a spot substrate assay and demonstrated that CSPGs have a repulsive effect on cell bodies as well as neurites of the postnatal cerebellar granule neurons (CGNs) in vitro. Through a brief inhibitor screen, we observed that the effects of CSPGs were abolished in the presence of mitogen-activated protein kinase (MAPK) inhibitor or epidermal growth factor receptor (EGFR) inhibitor. The MAPK pathway was activated in the neurons treated with CSPGs, and this activation was dependent on EGFR. Thus, CSPGs triggered the inhibition of CGNs through the activation of the EGFR-mediated MAPK pathway.