Neurite outgrowth inhibition by chondroitin sulfate proteoglycan: Stalling/stopping exceeds turning in human neuroblastoma growth cones

Chondroitin sulfate proteoglycan (CSPG) inhibits outgrowth from embryonic c hick and rodent neurons in vivo and in vivo and is upregulated during devel opment and following injury, The role of CSPG; in outgrowth from human neur ons has been largely untested, but is critical for our understanding of reg eneration in humans following nervous system injury. Here we determined the effects of CSPG on platelet-derived growth factor (PDGF)-stimulated neurit e outgrowth from SH-SY5Y human neuroblastoma cells, a well-accepted model o f neuronal differentiation. Cells were plated on glass coverslips adsorbed with laminin (LN), CSPG, or a patterned substratum consisting of alternatin g stripes of the two molecules. Similar to other studies using chick or rod ent neurons, SH-SY5Y cells extend neurites on LN, displaying a 15.2% increa se in the total neurite length/cell as compared to cells plated on glass. C ells plated on CSPG: alone exhibited reduced neurite outgrowth compared to cells plated on glass or LN. interestingly, SH-SY5Y growth cones extending on LN and then encountering a CSPG: border display more stopping/stalling ( 62.3%) than turning (27.9%) behaviors. Soluble CSPG: inhibits neurite initi ation from SH-SY5Y cells plated on glass, but not on LN. These data demonst rate that several CSPG-elicited responses of human neuron-like cells are si milar to those from nonhuman neurons. However, approximately 70% of SH-SY5Y growth cones sfop or stall at a CSPG border while over 80% of chick sensor y neurons turn at a CSPG border. The experimental difference between these models may well indicate a functional difference between animal and human n euronal regeneration. (C) 1999 Academic Press.