Schwann cell chondroitin sulfate proteoglycan inhibits dorsal root ganglion neuron neurite outgrowth and substrate specificity via a soma and not a growth cone mechanism.
Sensory axons do not regenerate into or within the spinal cord because of the presence of the axon regeneration inhibitor chondroitin sulfate proteoglycan (CSPG) on activated astrocytes. In the peripheral nervous system, CSPG associated with denervated Schwann cells retards axon regeneration, but regeneration occurs because the balance of regenerating, inhibiting, and promoting factors favors regeneration. The present experiments were aimed at determining the mechanism by which Schwann cells inhibit adult human dorsal root ganglia (H-DRG) neuron growth cone elongation and substrate specificity, restricting the growth cones to Schwann cell membranes and inhibiting their growth onto a poly-l-lysine/laminin substrate. Neurites of H-DRG neurons free of soma contact with Schwann cells, or after the Schwann cell membranes' CSPG had been digested, were 11.1-fold longer than those of neurons in soma contact with untreated Schwann cells. Growth cones of DRG neuron somas without Schwann cell CSPG showed no outgrowth inhibition or substrate specificity. These results indicate that the Schwann cell CSPG influences act via contact with neuron somas but not growth cones. These results suggest that eliminating CSPG associated with Schwann cells within DRG in vivo will make the neurons' growth cones insensitive to the regeneration inhibitory influences of CSPG, allowing them to regenerate through the dorsal root entry zone and into and within the spinal cord, where they can establish appropriate and functional synaptic connections.
Kuffler
Damien P
DP
Institute of Neurobiology, Section of Neurosurgery, University of Puerto Rico, San Juan, Puerto Rico. dkuffler@hotmail.com
Sosa
Ivan J
IJ
Reyes
Onix
O
D000328:Adult; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D019765:Chondroitin ABC Lyase / Q000494:pharmacology*; D011508:Chondroitin Sulfate Proteoglycans / Q000494:pharmacology*; D018920:Coculture Techniques; D005727:Ganglia, Spinal / Q000166:cytology*; D020439:Growth Cones / Q000502:physiology; D006801:Humans; D008959:Models, Neurological; D009416:Nerve Regeneration / Q000502:physiology; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D012583:Schwann Cells / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000648:ultrastructure; D013379:Substrate Specificity / Q000187:drug effects
D011508:Chondroitin Sulfate Proteoglycans; D019765:Chondroitin ABC Lyase