Human central nervous system myelin inhibits neurite outgrowth.
In vitro and animal studies have identified molecules in mammalian CNS myelin which inhibit neuritic extension and which may be responsible, at least in part, for the lack of axonal regeneration after injury in the injured brain, optic nerve and spinal cord. To determine whether such inhibitory activity may be present in human CNS myelin, we used a bioassay to characterize neurite outgrowth on this substrate. Human CNS myelin strongly inhibited neuritic outgrowth from newborn rat dorsal root ganglion neurons and NG-108-15 cells, a neuroblastoma-glioma hybrid cell line. Similar but less potent inhibitory activity was identified in human gray matter. The CNS myelin inhibition of neuritic outgrowth appeared to be dependent on direct contact between the myelin substrate and neurites. The inhibitory activity in human CNS myelin closely resembled that described in adult rodents. Inhibition of neurite growth by human CNS myelin in this in vitro bioassay mirrors the lack of regeneration in vivo and can be used as a model to develop strategies designed to enhance axonal regeneration and neural recovery.
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Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.
Cartel
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N
Roder
J
J
Roach
A
A
Lozano
A
A
D000368:Aged; D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D015153:Blotting, Western; D001921:Brain / Q000502:physiology* / Q000648:ultrastructure; D002478:Cells, Cultured; D003337:Corpus Callosum / Q000502:physiology; D005727:Ganglia, Spinal / Q000166:cytology; D006801:Humans; D008297:Male; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000502:physiology*; D016501:Neurites / Q000502:physiology* / Q000648:ultrastructure; D010487:Periaqueductal Gray / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014357:Trypsin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004676:Myelin Basic Protein; D014357:Trypsin