Differential regulation of neuronal proteoglycans by activation of excitatory amino acid receptors.

Cell surface proteoglycans (PGs) have been implicated in neuronal growth, migration and differentiation and can play pivotal roles both in cell-cell and cell-substrate interactions during the development of the nervous system. We have previously shown that glutamate activation of excitatory amino acid receptors induces the synthesis and release of PGs with neurite-promoting activity from hippocampal neurones. In this study, we have investigated the activity-dependent regulation of mRNA expression of two PGs in fetal hippocampal neurones using a competitive reverse transcriptase-polymerase chain reaction and correlated this expression with neuronal growth. Both cerebroglycan (CBG), a glycosylphatidylinositol-anchored heparan sulphate PG, and neurocan, a developmentally regulated chondroitin sulphate PG, are expressed in hippocampal neurones. Exposure of hippocampal neurones to 100 microM glutamate for 5 min resulted in an increase in CBG mRNA levels and an increase in axonal and dendritic length. The increase in CBG mRNA levels following glutamate exposure was mediated via both N-methyl-D-aspartate and metabotropic receptor activation.