Sun Y, Zigmond R E
Department of Neurosciences, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106-4975, USA.
J Neurochem. 1996 Oct;67(4):1751-60. doi: 10.1046/j.1471-4159.1996.67041751.x.
In response to axonal injury, noradrenergic sympathetic neurons of the adult superior cervical ganglion (SCG) alter their neurotransmitter phenotype. These alterations include increases in the levels of the neuropeptides, galanin, vasoactive intestinal peptide (VIP), and substance P (SP) and a decrease in the catecholamine biosynthetic enzyme tyrosine hydroxylase (TH). Previous studies have indicated that after axotomy in vivo, leukemia inhibitory factor (LIF) plays an important role in increasing the contents of galanin and VIP in the SCG. In the present study, by examining the time courses of the changes in LIF and neuropeptide mRNA and by using LIF null mutant mice, we have determined that LIF alters neuropeptide content in part by increasing levels of peptide mRNA. In addition, LIF also makes a small contribution to the axotomy-induced down-regulation of mRNA encoding TH and neuropeptide Y, both of which are normally expressed at high levels in the SCG. Finally, by using a LIF-blocking antiserum, this cytokine was found to regulate SP expression in an in vitro axonal injury model. Thus, after axotomy, a single factor, LIF, participates in the down-regulation of peptides/proteins involved in normal neurotransmission and the up-regulation of a group of neuropeptides normally not present in the SCG that may be involved in regeneration.
作为对轴突损伤的反应，成年颈上神经节（SCG）的去甲肾上腺素能交感神经元会改变其神经递质表型。这些改变包括神经肽、甘丙肽、血管活性肠肽（VIP）和P物质（SP）水平的升高，以及儿茶酚胺生物合成酶酪氨酸羟化酶（TH）水平的降低。先前的研究表明，在体内进行轴突切断术后，白血病抑制因子（LIF）在增加SCG中甘丙肽和VIP的含量方面发挥重要作用。在本研究中，通过检测LIF和神经肽mRNA变化的时间进程，并使用LIF基因敲除突变小鼠，我们确定LIF部分通过增加肽mRNA水平来改变神经肽含量。此外，LIF对轴突切断诱导的TH和神经肽Y编码mRNA的下调也有小部分贡献，这两种物质在SCG中通常高水平表达。最后，通过使用LIF阻断抗血清，发现这种细胞因子在体外轴突损伤模型中调节SP表达。因此，轴突切断后，单一因子LIF参与了正常神经传递中涉及的肽/蛋白质的下调以及SCG中通常不存在但可能参与再生的一组神经肽的上调。
