Axonal reinjury reveals the survival and re-expression of regeneration-associated genes in chronically axotomized adult mouse motoneurons

Exp Neurol. 2004 Aug;188(2):331-40. doi: 10.1016/j.expneurol.2004.04.010.


Recently, we reported that chronically axotomized rubrospinal neurons survive for up to 1 year in an atrophied state. This finding contrasted previous work suggesting the death of up to 50% of the neurons over time. In the adult mouse, the majority of facial motoneurons appear to be lost as a result of chronic nerve resection. Here, we sought to determine if chronically resected adult mouse facial motoneurons, like rubrospinal neurons, survive in an atrophied state. To test this hypothesis, we asked whether a second nerve injury, 10 weeks after an initial nerve resection, could stimulate a regenerative cell body response. After chronic resection (10 weeks), mouse facial motoneurons underwent atrophy resulting in a loss of countable neuronal cell bodies. In addition, the motoneurons failed to maintain their initial increase in expression of GAP-43 and alpha-tubulin mRNA. Reinjury of 10-week chronically resected facial motoneurons by the removal of the neuroma reversed the atrophy of the cell bodies and increased the percentage of identifiable cell bodies from 36% of contralateral to 79% in C57BL/6-C3H mice and from 28% of contralateral to 40% in Balb/c mice. Moreover, the reinjured motoneurons displayed an increase in GAP-43 and alpha-tubulin mRNA expression. The results of this study indicate that a second axon injury stimulates regenerative cell body responses in chronically resected mouse facial motoneurons and suggest previous studies using this model may have overestimated the number of dying motoneurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Outbred Strains
  • Axons / metabolism*
  • Axons / pathology
  • Axotomy
  • Cell Count
  • Chronic Disease
  • Disease Models, Animal
  • Facial Nerve Injuries / genetics*
  • Facial Nerve Injuries / metabolism*
  • Facial Nerve Injuries / pathology
  • Fluorescent Dyes
  • GAP-43 Protein / genetics
  • Immunohistochemistry
  • In Situ Hybridization
  • Mice
  • Mice, Inbred Strains
  • Motor Neurons / metabolism*
  • Motor Neurons / pathology
  • Nerve Regeneration / genetics*
  • RNA, Messenger / metabolism
  • Recurrence
  • Species Specificity
  • Stilbamidines
  • Tubulin / genetics


  • 2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt
  • Fluorescent Dyes
  • GAP-43 Protein
  • RNA, Messenger
  • Stilbamidines
  • Tubulin