Ciliary neurotrophic factor is an early lesion-induced retrograde signal for axotomized facial motoneurons.
To investigate the involvement of ciliary neurotropic factor (CNTF) in the postlesional response of motoneurons, we studied the activation of STAT3 signaling, the main signal transduction pathway of CNTF-like cytokines, in the facial nucleus of wildtype and CNTF-deficient mice following peripheral nerve transection. As shown by immunocytochemistry and immunoblot analysis, phosphorylation and nuclear translocation of STAT3 was maximally induced within 12 h postlesion in motoneurons of the ipsilateral facial nucleus of wildtype mice and is maintained for at least 3 days. In CNTF(-/-) mouse mutants, activation of STAT3 signaling was delayed by 10-12 h. Application of CNTF to the transected nerve restored rapid STAT3 activation in CNTF-deficient animals, whereas application of colchicine suppressed STAT3 signaling in wildtype mice for at least 24 h. These results identify CNTF as an early retrograde signal in axotomized facial motoneurons by showing that CNTF released at the lesion site is responsible for the initial induction of STAT3 signaling. Other cytokines like leukemia inhibitory factor obviously become active at later time points.
Kirsch
Matthias
M
Institute of Anatomy, University of Freiburg, P.O. Box 111, D-79001 Freiburg, Germany.
Terheggen
Ulrich
U
Hofmann
Hans-Dieter
HD
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D019771:Axotomy; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D020934:Ciliary Neurotrophic Factor / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D003078:Colchicine / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D005154:Facial Nerve / Q000166:cytology / Q000378:metabolism*; D020220:Facial Nerve Injuries / Q000378:metabolism* / Q000503:physiopathology; D015850:Interleukin-6 / Q000378:metabolism; D053605:Leukemia Inhibitory Factor; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012183:Retrograde Degeneration / Q000378:metabolism / Q000503:physiopathology; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism
D020934:Ciliary Neurotrophic Factor; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D003078:Colchicine