The dependence on gp130 cytokines of axotomy induced neuropeptide expression in adult sympathetic neurons.
Adult peripheral neurons exhibit dramatic changes in gene expression after axonal injury, including changes in neuropeptide phenotype. For example, sympathetic neurons in the superior cervical ganglion (SCG) begin to express vasoactive intestinal peptide (VIP), galanin, pituitary adenylate cyclase activating polypeptide (PACAP), and cholecystokinin after axotomy. Before these changes, nonneuronal cells in the SCG begin to express leukemia inhibitory factor (LIF). When the effects of axotomy were compared in LIF-/- and wild-type mice, the increases in VIP and galanin expression were less in the former, though significant increases still occurred. LIF belongs to a family of cytokines with overlapping physiological effects and multimeric receptors containing the subunit gp130. Real-time PCR revealed large increases in the SCG after axotomy in mRNA for three members of this cytokine family, interleukin (IL)-6, IL-11, and LIF, with modest increases in oncostatin M, no changes in ciliary neurotrophic factor, and decreases in cardiotrophin-1. To explore the role of these cytokines, animals with selective elimination of the gp130 receptor in noradrenergic neurons were studied. No significant changes in mRNA levels for VIP, galanin, and PACAP were seen in axotomized ganglia from these mutant mice, while the increase in cholecystokinin was as large as that seen in wild-type mice. The data indicate that the inductions of VIP, galanin, and PACAP after axotomy are completely dependent on gp130 cytokines and that a second cytokine, in addition to LIF, is involved. The increase in cholecystokinin after axotomy, however, does not require the action of these cytokines.
Habecker
Beth A
BA
Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, Oregon 97239-3098, USA.
Sachs
Hilary Hyatt
HH
Rohrer
Hermann
H
Zigmond
Richard E
RE
D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D019771:Axotomy / Q000379:methods; D002766:Cholecystokinin / Q000235:genetics / Q000378:metabolism; D050822:Cytokine Receptor gp130 / Q000172:deficiency / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D017783:Superior Cervical Ganglion / Q000166:cytology*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism
D051700:Activating Transcription Factor 3; C103002:Atf3 protein, mouse; C494200:Il6st protein, mouse; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D050822:Cytokine Receptor gp130; D014660:Vasoactive Intestinal Peptide; D002766:Cholecystokinin; D014446:Tyrosine 3-Monooxygenase