The conditioning lesion effect on sympathetic neurite outgrowth is dependent on gp130 cytokines

• Published in: Experimental neurology 2010-06, Vol.223 (2), p.516-522
• Main Authors: Hyatt Sachs, H., Rohrer, H., Zigmond, R.E.
• Format: Article
• Language: English
• Subjects: Activating Transcription Factor 3 - metabolism; Animals; Axotomy; Biological and medical sciences; Cells, Cultured; Conditioning lesion; Cytokine; Cytokine Receptor gp130 - genetics; Cytokine Receptor gp130 - metabolism; Female; Fundamental and applied biological sciences. Psychology; gp130; Interleukin-6; Interleukin-6 - metabolism; Isolated neuron and nerve. Neuroglia; Leukemia inhibitory factor; Leukemia Inhibitory Factor - metabolism; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurite outgrowth; Neurites - physiology; Neurology; Phosphorylation - physiology; Regeneration; Signal Transduction - physiology; STAT3 Transcription Factor - metabolism; Superior cervical ganglion; Superior Cervical Ganglion - cytology; Superior Cervical Ganglion - physiology; Sympathetic; Vertebrates: nervous system and sense organs
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2010.01.019

Sympathetic neurons, like sensory neurons, increase neurite outgrowth after a conditioning lesion. Studies in leukemia inhibitory factor (LIF) knockout animals showed that the conditioning lesion effect in sensory neurons is dependent in part on this cytokine; however, similar studies on sympathetic neurons revealed no such effect. Comparable studies with sensory neurons taken from mice lacking the related cytokine interleukin-6 (IL-6) have yielded conflicting results. LIF and IL-6 belong to a family of cytokines known as the gp130 family because they act on receptors containing the subunit gp130. In sympathetic ganglia, axotomy leads to increases in mRNA for four of these cytokines (LIF, IL-6, IL-11, and oncostatin M). To test the role of this family of cytokines as a whole in the conditioning lesion response in sympathetic neurons, mice in which gp130 was selectively eliminated in noradrenergic neurons were studied. The postganglionic axons of the SCG were transected, and 7 days later the ganglia were removed and neurite outgrowth was measured in explant and dissociated cell cultures. In both systems, neurons from wild type animals showed enhanced growth after a conditioning lesion. In contrast, no enhancement occurred in neurons from mutant animals. This lack of stimulation of outgrowth occurred despite an increase in expression of activating transcription factor 3 (ATF3) in the mutant mice. These studies demonstrate that stimulation of enhanced growth of sympathetic neurons after a conditioning lesion is dependent on gp130 cytokine signaling and is blocked in the absence of signaling by these cytokines in spite of an increase in ATF3.