Increased production of ubiquitin mRNA in motor neurons after axotomy

Ubiquitin targets proteins for attack by certain proteolytic enzymes, but the ubiquitinated cytoplasmic inclusions seen in some chronic neurodegenerative diseases may indicate the occurrence of reparative rather than destructive metabolic events. We have examined the production of ubiquitin in motor neurons of the rat's left hypoglossal nucleus after transection of their axons in circumstances that favour or prevent axonal regeneration. One week after axotomy, in situ hybridization with a radiolabelled cRNA probe revealed a twofold increase in the ubiquitin mRNA content of neurons with regenerating axons (nerve crushed) but not significant change when axonal regeneration had been prevented (nerve transected and ligated). After 2 weeks, ubiquitin mRNA was elevated to about 1.5 times the contralateral control level, regardless of the type of nerve injury, and by 4 weeks there were no longer any differences between the left and right sides. Despite the increased transcription, axotomy was not followed by any change in the quantity of ubiquitin-immunoreactive material in the nuclei or perikarya of hypoglossal neurons as measured by video image analysis of immunohistochemically stained sections. We suggest that ubiquitin is synthesized in neuronal cell bodies and transported into their axons, and that ubiquitin-mediated proteolysis is a metabolic process involved in the elongation of regenerating axons.