MYELIN-ASSOCIATED GLYCOPROTEIN INHIBITS NEURITE AXON GROWTH AND CAUSES GROWTH CONE COLLAPSE/

We have previously shown that myelin-associated glycoprotein (MAG) inh ibits neurite growth from a neuronal cell line, In this study we show that 60% of axonal growth cones of postnatal day 1 hippocampal neurons collapsed when they encountered polystyrene beads coated with recombi nant MAG (rMAG), Such collapse was not observed with denatured rMAG, N eurite growth from rat embryonic hippocampal and neonatal cerebellar n eurons was also inhibited about 80% on tissue culture substrates coate d with rMAG, To investigate further the inhibitory activity of MAG in myelin, we purified myelin from MAG-deficient mice and separated octyl glucoside extracts of myelin by diethylaminoethyl (DEAE) ion-exchange chromatography, Although there was no significant difference in neurit e growth on myelin purified from MAG-/- and MAG+/+ mice, differences w ere observed in the fractionated material, The major inhibitory peak t hat is associated with MAG in normal mice was significantly reduced in MAG-deficient mice, These results suggest that although MAG contribut es significantly to axon growth inhibition associated with myelin, its lack in MAG-deficient mice is masked by other non-MAG inhibitors, Axo n regeneration in these mice was also examined after thoracic lesions of the corticospinal tracts. A very small number of anterogradely labe led axons extended up to 13.2 mm past the lesion in MAG-/- mice, Altho ugh there is some enhancement of axon generation, the poor growth afte r spinal cord injury in MAG-/- mice may be due to the presence of othe r non-MAG inhibitors, The in vitro studies, however, provide the first evidence that MAG modulates growth cone behavior and inhibits neurite growth by causing growth cone collapse. (C) 1996 Wiley-Liss, Inc.