Actions of neuropoietic cytokines and cyclic AMP in regenerative conditioning of rat primary sensory neurons.
A conditioning lesion to peripheral axons of primary sensory neurons accelerates regeneration of their central axons in vivo or neurite outgrowth if the neurons are grown in vitro. Previous evidence has implicated neuropoietic cytokines and also cyclic AMP in regenerative conditioning. In experiments reported here, delivery through a lentivirus vector of ciliary neurotrophic factor to the appropriate dorsal root ganglion in rats was sufficient to mimic the conditioning effect of peripheral nerve injury on the regeneration of dorsal spinal nerve root axons. Regeneration in this experimental preparation was also stimulated by intraganglionic injection of dibutyryl cyclic AMP but the effects of ciliary neurotrophic factor and dibutyryl cyclic AMP were not additive. Dibutyryl cyclic AMP injection into the dorsal root ganglion induced mRNAs for two other neuropoietic cytokines, interleukin-6 and leukemia inhibitory factor and increased the accumulation of phosphorylated STAT3 in neuronal nuclei. The in vitro conditioning action of dibutyryl cyclic AMP was partially blocked by a pharmacological inhibitor of Janus kinase 2, a neuropoietic cytokine signaling molecule. We suggest that the beneficial actions of increased cyclic AMP activity on axonal regeneration of primary sensory neurons are mediated, at least in part, through the induction of neuropoietic cytokine synthesis within the dorsal root ganglion.
Wu
Dongsheng
D
Center for Neuroscience, Institute of Cell and Molecular Sciences, Barts and The London, Queen Mary's School of Medicine, University of London, 4 Newark Street, London E1 2AT, UK.
Zhang
Yi
Y
Bo
Xuenong
X
Huang
Wenlong
W
Xiao
Fang
F
Zhang
Xinyu
X
Miao
Tizong
T
Magoulas
Charalambos
C
Subang
Maria C
MC
Richardson
Peter M
PM
D000818:Animals; D001369:Axons / Q000502:physiology; D003994:Bucladesine / Q000494:pharmacology; D020934:Ciliary Neurotrophic Factor / Q000235:genetics / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D015850:Interleukin-6 / Q000235:genetics; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors; D016086:Lentivirus / Q000235:genetics; D053605:Leukemia Inhibitory Factor / Q000235:genetics; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013126:Spinal Nerve Roots; D020032:Tyrphostins / Q000494:pharmacology
D020934:Ciliary Neurotrophic Factor; D016207:Cytokines; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D012333:RNA, Messenger; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D003994:Bucladesine; D000242:Cyclic AMP; C507927:Jak2 protein, rat; D053614:Janus Kinase 2