Selective impairment of slow axonal transport after optic nerve injury in adult rats.
To investigate cellular responses of injured mammalian CNS neurons, we examined the slow transport of cytoskeletal proteins in rat retinal ganglion cell (RGC) axons within the ocular stump of optic nerves that were crushed intracranially. RGC proteins were labeled by an intravitreal injection of 35S-methionine, and optic nerves were examined by SDS PAGE at different times after injury. In one group of rats, the RGC proteins were labeled 1 week after crushing. From 14 to 67 d after axotomy, the labeling of tubulin and neurofilaments was reduced in relation to other labeled proteins and to the labeling of tubulin and neurofilaments in the intact optic nerve of controls. To determine whether this reduction in labeling was due to an alteration in axonal transport after axotomy, we prelabeled RGC proteins 1 week before crushing. In such experiments, the rate of slow axonal transport of tubulin and neurofilaments decreased approximately 10-fold from 6 to 60 d after injury. Our results cannot be due only to the retrograde degeneration of RGCs and injured axons caused by axotomy in the optic nerve, because fast axonal protein transport and the fluorescent labeling of many axons were preserved in the ocular stumps of these optic nerves. This selective failure of the slow axonal transport of tubulin and neurofilaments may affect the renewal of the cytoskeleton and contribute to the gradual degeneration of RGCs that is observed after axotomy. The alterations in slow transport we document here differ from the enhanced rates we previously reported when injured RGC axons regenerated along peripheral nerve segments grafted to the ocular stump of transected optic nerves (McKerracher et al., 1990).
Center for Research in Neuroscience, Montreal General Hospital Research Institute, Quebec, Canada.
L
L
McKerracher
M
M
Vidal-Sanz
C
C
Essagian
A J
AJ
Aguayo
D000818:Animals; D001370:Axonal Transport; D001692:Biological Transport; D002470:Cell Survival; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005260:Female; D007381:Intermediate Filament Proteins / Q000378:metabolism; D009409:Nerve Crush; D016900:Neurofilament Proteins; D009900:Optic Nerve / Q000378:metabolism; D020221:Optic Nerve Injuries; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism
D003598:Cytoskeletal Proteins; D007381:Intermediate Filament Proteins; D016900:Neurofilament Proteins; D014404:Tubulin