Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland OH, 44106-4975, USA.
Exp Neurol. 2010 Jun;223(2):516-22. doi: 10.1016/j.expneurol.2010.01.019. Epub 2010 Feb 8.
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 7days 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.
交感神经元与感觉神经元一样，在条件性损伤后会增加神经突生长。白血病抑制因子（LIF）敲除动物的研究表明，感觉神经元的条件性损伤效应部分依赖于这种细胞因子；然而，对交感神经元的类似研究并未显示出这种效应。用缺乏相关细胞因子白细胞介素-6（IL-6）的小鼠的感觉神经元进行类似的研究得出了相互矛盾的结果。LIF 和 IL-6 属于细胞因子家族的 gp130 家族，因为它们作用于含有亚基 gp130 的受体。在交感神经节中，轴突切断导致其中四种细胞因子（LIF、IL-6、IL-11 和肿瘤坏死因子 M）的 mRNA 增加。为了测试整个 gp130 家族细胞因子作为交感神经元条件性损伤反应的一部分的作用，研究了在去甲肾上腺素能神经元中选择性消除 gp130 的小鼠。切断 SCG 的节后轴突，7 天后取出神经节，在离体和分离细胞培养物中测量神经突生长。在这两种系统中，来自野生型动物的神经元在条件性损伤后表现出增强的生长。相比之下，突变动物的神经元没有增强。尽管突变小鼠中激活转录因子 3（ATF3）的表达增加，但这种生长的缺乏刺激仍未发生。这些研究表明，交感神经元在条件性损伤后增强生长的刺激依赖于 gp130 细胞因子信号，并且在这些细胞因子的信号缺失时尽管 ATF3 增加但不会发生。
