Actions of neuropoietic cytokines and cyclic AMP in regenerative conditioning of rat primary sensory neurons

• Published in: Experimental neurology Vol. 204; no. 1; pp. 66 - 76
• Main Authors: Wu, Dongsheng, Zhang, Yi, Bo, Xuenong, Huang, Wenlong, Xiao, Fang, Zhang, Xinyu, Miao, Tizong, Magoulas, Charalambos, Subang, Maria C., Richardson, Peter M.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.03.2007; Elsevier
• Subjects: Animals; Axon regeneration; Axons - physiology; Biological and medical sciences; Bucladesine - pharmacology; cAMP; Ciliary Neurotrophic Factor - genetics; Ciliary Neurotrophic Factor - pharmacology; CNTF; Conditioning; Conditioning (Psychology) - drug effects; Conditioning (Psychology) - physiology; Cyclic AMP - metabolism; Cytokines - metabolism; Enzyme Inhibitors - pharmacology; Ganglia, Spinal; Gene Expression Regulation; Gene Transfer Techniques; Genetic Vectors; Injuries of the nervous system and the skull. Diseases due to physical agents; Interleukin-6 - genetics; Janus Kinase 2 - antagonists & inhibitors; Lentivirus; Lentivirus - genetics; Leukemia Inhibitory Factor - genetics; Medical sciences; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Nerve Crush; Nerve Regeneration - genetics; Nerve Regeneration - physiology; Neurology; Neurons, Afferent - drug effects; Neurons, Afferent - metabolism; Neurons, Afferent - physiology; Primary sensory neuron; Rats; Rats, Sprague-Dawley; Recombinant Proteins - pharmacology; RNA, Messenger - biosynthesis; Signal Transduction; Spinal Nerve Roots; STAT3 Transcription Factor - metabolism; Traumas. Diseases due to physical agents; Tyrphostins - pharmacology; PBS; TU; CNTF; LIF; dbcAMP; LV; cAMP; IL-6; GFP; JAK; Axon regeneration; Primary sensory neuron; DRG; Conditioning; Peripheral nerve; Spinal cord; Phosphorylation; Neurite; Rat; Central nervous system; Ciliary neurotrophic factor; Spinal nerve; Spinal root; Interleukin 6; Signal transduction; Vector; Enzyme; Mimic; Transferases; Leukemia inhibitory factor; Rodentia; Cytokine; Retroviridae; Cyclic AMP; Axon; Posterior spinal root; Lentivirus; Virus; Regeneration; Vertebrata; Mammalia; Kinase; Animal; Preparation; Sensory neuron; Spinal ganglion
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2006.09.017

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.