Tubulin expression and axonal transport in injured and regenerating neurons in the adult mammalian central nervous system.

Microtubules are essential components of the cytoskeleton required for axonal growth. To investigate how changes in tubulin transport and expression may affect axon regeneration, injury in the adult mammalian central nervous system was studied. Axotomized retinal ganglion cells (RGCs) that do not regenerate were compared with RGCs that regenerate their axons when the optic nerve is replaced with a peripheral nerve graft. When RGC axons regenerated through peripheral nerve grafts, the rate of slow transport increased but decreased when no regrowth occurred. To investigate the molecular mechanisms that mediate these responses, alterations in tubulin mRNA levels after injury were examined. Total tubulin mRNA levels fell after injury in the optic nerve but increased in those RGCs that regenerated their axons into a peripheral nerve graft. Further, the expression of four separate beta-tubulin isotypes in injured rat RGCs was characterized. mRNA levels for all four isotypes decreased in RGCs after injury in the optic nerve. How the autoregulation of tubulin expression may contribute to the changes in beta-tubulin isotype expression after injury is discussed.