Nervous system-derived chondroitin sulfate proteoglycans regulate growth cone morphology and inhibit neurite outgrowth: A light, epifluorescence, andelectron microscopy study

Proteoglycans influence aging and plasticity in the nervous system. Particu larly prominent are the chondroitin sulfate proteoglycans (CSPGs), which ar e generally inhibitory to neurite outgrowth. During development, CSPGs faci litate normal guidance, but following nervous system injury and in diseases of aging (e.g., Alzheimer's disease), they block successful regeneration, and are associated with axon devoid regions and degenerating nerve cells. W hereas previous studies used non-nervous system sources of CSPGs, this stud y analyzed the morphology and behavior of sensory (dorsal root ganglia) neu rons, and a human nerve cell model (SH-SY5Y neuroblastoma cells) as they co ntacted nervous system-derived CSPGs, using a variety of microscopy techniq ues. The results of these qualitative analyses show that growth cones of bo th nerve cell types contact CSPGs via actin-based filopodia, sample the CSP Gs repeatedly without collapse, and alter their trajectory to avoid nervous system-derived CSPGs. Turning and branching are correlated with increased filopodial sampling, and are common to both neurons and Schwann cells. We s how that CSPG expression by rat CNS astrocytes in culture is correlated wit h sensory neuron avoidance. Further, we show for the first time the ultrast ructure of sensory growth cones at a CSPG-laminin border and reveal details of growth cone and neurite organization at this choice point. This type of detailed analysis of the response of growth cones to nervous system-derive d CSPGs may lead to an understanding of CSPG function following injury and in diseases of aging, where CSPGs are likely to contribute to aberrant neur ite outgrowth, failed or reduced synaptic connectivity, and/or ineffective plasticity. Microsc. Res. Tech. 54:273-286, 2001. (C) 2001 Wiley-Liss, Inc.