Sun Y, Zigmond R E
Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-4975, USA.
Eur J Neurosci. 1996 Oct;8(10):2213-20. doi: 10.1111/j.1460-9568.1996.tb00744.x.
Dramatic changes occur in neuropeptide expression in sensory and sympathetic neurons following axonal injury. Based on the finding that the cytokine leukemia inhibitory factor (LIF) plays an important role in mediating these changes in sympathetic neurons, its participation in triggering changes in sensory neurons was examined. By the use of transgenic mice in which the LIF gene had been knocked out, LIF was found to contribute to the induction of galanin expression in dorsal root ganglia (DRG) after sciatic nerve lesion. On the other hand, two other neuropeptide changes that occur in DRG under these conditions, the reduction of substance P and induction of neuropeptide Y, were independent of LIF expression. In the sympathetic superior cervical ganglion, transection of the postganglionic nerves close to the ganglion resulted in a rapid induction of LIF mRNA in the ganglion and in the lesioned nerve trunk. In contrast, transection of the sciatic nerve close to or distant from the DRG caused a rapid induction of LIF mRNA in the lesioned nerve, but not in the DRG. DRG were capable of making substantial amounts of LIF mRNA when placed in explant cultures, but, in vivo, only a slight induction was found even when both central and peripheral nerve processes of these sensory neurons were transected. These latter observations suggest that, in contrast to the superior cervical ganglia, the DRG environment inhibits the lesion-induced expression of LIF in vivo and/or explanted DRG produce stimulatory signals not found in vivo. Together with the data on the induction of galanin, these observations provide evidence that LIF, generated at a site at some distance from the ganglion, is involved in triggering part of the cell body reaction in sensory neurons.
轴突损伤后，感觉神经元和交感神经元中的神经肽表达会发生显著变化。基于细胞因子白血病抑制因子（LIF）在介导交感神经元这些变化中起重要作用这一发现，研究了其在触发感觉神经元变化中的作用。通过使用LIF基因敲除的转基因小鼠，发现LIF有助于坐骨神经损伤后背根神经节（DRG）中甘丙肽表达的诱导。另一方面，在这些条件下DRG中发生的另外两种神经肽变化，即P物质的减少和神经肽Y的诱导，与LIF表达无关。在交感神经颈上神经节中，靠近神经节的节后神经横断导致神经节和损伤的神经干中LIF mRNA迅速诱导。相反，靠近或远离DRG的坐骨神经横断导致损伤神经中LIF mRNA迅速诱导，但DRG中没有。当置于外植体培养中时，DRG能够产生大量的LIF mRNA，但在体内，即使这些感觉神经元的中枢和外周神经突起都被横断，也仅发现轻微的诱导。这些观察结果表明，与颈上神经节不同，DRG环境在体内抑制损伤诱导的LIF表达，和/或外植的DRG产生体内未发现的刺激信号。连同关于甘丙肽诱导的数据，这些观察结果提供了证据，表明在距神经节一定距离的部位产生的LIF参与触发感觉神经元中的部分细胞体反应。
