Proteolysis is a critical step in the physiological stop pathway: mechanisms involved in the blockade of axonal regeneration by mammalian astrocytes.
Regenerating axons of adult dorsal roots are stopped by reactive astrocytes at the PNS-CNS junction. While it has been suggested that the astrocytes might pose a physical barrier to axonal growth, based on ultrastructural comparisons of physically blocked and axo-glial endings, it was proposed that astrocytes in the root transitional zone block axonal growth by activating the physiological stop pathway within the growing axon tips. Part of the stop pathway involves the proteolytic breakdown and removal of neurofilaments as they enter the axon endings. Another component involves the establishment of anterograde-to-retrograde conversion for the removal of membranous elements from the axonal endings. Both of these components appear to be dependent upon the activation of proteases within the axon tips. Therefore, to further test our hypothesis we infused, by intrathecal catheterization, the region of the dorsal root transitional zone with the protease inhibitor leupeptin at a time when the majority of regenerating axons have terminated in the region. Ultrastructural analyses after leupeptin treatment revealed axo-glial endings distended by accumulations of neurofilaments and organelles, particularly tubulovesicular profiles. These observations further support the idea that astrocytes, like normal target cells, can activate the physiological stop pathway.
Liuzzi
F J
FJ
Department of Anatomy and Cell Biology, Eastern Virginia Medical School, Norfolk 23501.
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007278:Injections, Spinal; D007976:Leupeptins / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron; D009411:Nerve Endings / Q000502:physiology / Q000648:ultrastructure; D009416:Nerve Regeneration; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013126:Spinal Nerve Roots / Q000502:physiology* / Q000648:ultrastructure
D004791:Enzyme Inhibitors; D007976:Leupeptins; D009419:Nerve Tissue Proteins; D009842:Oligopeptides; C032854:leupeptin