A POTENT INHIBITOR OF NEURITE OUTGROWTH THAT PREDOMINATES IN THE EXTRACELLULAR-MATRIX OF REACTIVE ASTROCYTES

In a model of astrogliosis in vitro, cultured cortical astrocytes were triggered into a functionally reactive state by an immobilized fragme nt of the beta-amyloid peptide. Induced astrocytes produced an extrace llular matrix that inhibited the outgrowth of embryonic CNS axons. Wit hin the extracellular matrix deposited by reactive astrocytes, we foun d an overall increase in the deposition of chondroitin sulphate that a ccounted for the inhibition. Specifically, we have detected an increas ed biosynthesis of a small chondroitin/heparan sulphate proteoglycan t hat is a potent inhibitor of axon outgrowth. We further suggest that t his proteoglycan, or related molecules yet to be discovered, may play a role in gliosis-mediated regenerative failure of CNS axons. Copyrigh t (C) 1996 ISDN.