Cell body response to injury in motoneurons and primary sensory neurons of a mutant mouse, Ola (Wld), in which Wallerian degeneration is delayed.
We examined the response to axon injury in the facial motoneurons and dorsal root ganglion (DRG) neurons of C57BL/Ola (Wld) mice, compared with the responses of C57BL/6J mice. The peripheral nerves of Ola mutants undergo remarkably slowed and muted Wallerian degeneration after injury. The increase in GAP-43 mRNA levels in facial motoneurons and DRG neurons was similar in both strains of mice, as was the initial decrease in medium-weight neurofilament (NFM) mRNA in facial motoneurons, and the increase in JUN immunoreactivity in both types of neurons. However, the subsequent recovery to normal low levels of JUN and GAP-43 mRNA expression and high levels of NFM mRNA was delayed in Ola motoneurons. We ascribe this delay to the slow regeneration and target reinnervation of facial axons in the Ola mice. These results show that absence of rapid Wallerian degeneration does not affect the initial cell body response to axonal injury. They also provide further evidence that restoration of normal levels of expression of GAP-43 and NFM mRNAs is dependent on target reinnervation and/or trophic factors provided by the distal nerve. Impaired regeneration in the Ola mouse does not seem to be a consequence of a defective cell body response to injury, and our results illustrate the general principle that, even if there is a vigorous cell body response to injury, normal axonal regeneration requires the additional provision of a favorable environment for growth.
D000818:Animals; D001369:Axons / Q000502:physiology*; D015415:Biomarkers / Q000737:chemistry; D005154:Facial Nerve / Q000166:cytology; D005260:Female; D019922:GAP-43 Protein; D005727:Ganglia, Spinal / Q000166:cytology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009046:Motor Neurons / Q000473:pathology*; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000032:analysis; D016900:Neurofilament Proteins / Q000032:analysis*; D009475:Neurons, Afferent / Q000473:pathology*; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis; D014855:Wallerian Degeneration / Q000502:physiology*
D015415:Biomarkers; D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D016755:Proto-Oncogene Proteins c-jun