Inhibition of c-Jun phosphorylation reduces axonal outgrowth of adult rat nodose ganglia and dorsal root ganglia sensory neurons.

Summary, in English

The role of c-Jun activation for survival and regeneration of sensory neurons is unclear. Here we report that c-Jun N-terminal kinase (JNK)-mediated c-Jun activation is important for axonal outgrowth of sensory neurons in rat nodose and dorsal root ganglia (DRG). Peripheral severance of the vagus or the sciatic nerve resulted in a massive and rapid, but transient increase of the activated JNK (p-JNK) in neuronal nuclei, followed by c-Jun phosphorylation and activating transcription factor-3 (ATF3) induction. JNK inhibition by the selective JNK inhibitors SP600125 and (D)-JNKI1 did not affect neuronal survival in explanted or dissociated ganglia, but dramatically reduced axonal outgrowth, c-Jun activation, and ATF3 induction. Using retrograde labeling, we demonstrated that activated c-Jun (p-c-Jun) and ATF3 were associated with regenerative neurons. Taken together, our results suggest that JNK-mediated c-Jun activation is one of the first cell body reactions in response to nerve injury and that this activation and subsequent ATF3 induction are associated with axonal outgrowth.

• Författare: Charlotta Lindwall; Lars Dahlin; Göran Lundborg; Martin Kanje
• Avdelning/ar: Biologiska institutionen; Handkirurgi, Malmö; Funktionell zoologi
• Publiceringsår: 2004
• Språk: Engelska
• Sidor: 267-279
• Publikation/Tidskrift/Serie: Molecular and Cellular Neuroscience
• Volym: 27
• Issue: 3
• Länkar: http://dx.doi.org/10.1016/j.mcn.2004.07.001
• Dokumenttyp: Artikel i tidskrift
• Förlag: Elsevier
• Ämne: Surgery
• Status: Published
• Projekt: Nerve regeneration - signal transduktion mechanisms, timing and alternatives to nerve grafts
• Forskningsgrupp: Hand Surgery, Malmö
• ISBN/ISSN/Övrigt: ISSN: 1044-7431