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Keywords:

  • axotomy;
  • gpl30;
  • hypoglossal nerve;
  • JAK2;
  • JAKS;
  • regeneration;
  • rat

Abstract

Numerous studies have suggested that growth factors and cytokines play an important role in the survival of injured neurons and in neurite elongation. Therefore, intracellular signalling pathways activated by growth factors and cytokine receptors play an important role in neuronal survival or for the re-establishment of connection. Since the JAK (janus kinase)-STAT (signal transducers and activators of transcription) signal transduction pathway is known to play a major role in cytokine receptor signalling, we first examined regulation of JAK gene expression following peripheral nerve injury by in situ hybridization histochemistry. The rat hypoglossal nerve was axotomized unilaterally and the mRNA levels for JAKI, JAK2. JAK3 and TYK2 were examined in the hypoglossal nucleus at postoperative times ranging from 1 to 35 days. Among the JAK family members, JAK2 and JAK3 were substantially increased in injured hypoglossal motoneurons, whereas no significant increases were observed for JAK1 and TYK2. These changes were further confirmed by immunohistochemistry using antibodies specific to JAKP and JAK3. In addition, we examined the JAK2 and JAK3 associated cytokine receptor components, IL-2R y and gp130, which are common to various cytokine receptors. Among these, gp130 immunostaining was upregulated after nerve injury. This was also confirmed by in situ hybridization. These results suggest that the injured neuron prepares the molecular machinery involved in certain cytokine receptor signalling pathways at an early phase of the regenerative process, accelerating for the neuron to respond to cytokines that may regulate survival and/or neurite elongation.