The dependence on gp130 cytokines of axotomy induced neuropeptide expression in adult sympathetic neurons.

The dependence on gp130 cytokines of axotomy induced neuropeptide expression in adult sympathetic neurons.
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DOI:
10.1002/dneu.20706
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发表时间:
2009-05
影响因子:
3
通讯作者:
Zigmond, Richard E.
Zigmond, Richard E.
中科院分区:
医学3区
文献类型:
--
作者:
Habecker, Beth A.;Sachs, Hilary Hyatt;Rohrer, Hermann;Zigmond, Richard E.

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成人周围神经元在轴突损伤后表现出基因表达的巨大变化,包括神经肽表型的变化。例如,轴切术后,颈上神经节(SCG)中的交感神经元开始表达血管活性肠肽(VIP)、甘丙肽、垂体腺苷酸环化酶激活多肽(PACAP)和胆囊收缩素。在这些变化之前,SCG 中的非神经元细胞开始表达白血病抑制因子 (LIF)。当比较 LIF −/− 和野生型小鼠中轴切开术的效果时,前者的 VIP 和甘丙肽表达增加较少,但仍然出现显着增加。 LIF 属于具有重叠生理效应的细胞因子家族和含有 gp130 亚基的多聚体受体。实时 PCR 显示,轴切术后,该细胞因子家族的三个成员白细胞介素 (IL)-6、IL-11 和 LIF 的 mRNA 大幅增加,制瘤素 M 适度增加,睫状神经营养因子没有变化,心肌营养蛋白-1 减少。为了探索这些细胞因子的作用,对去甲肾上腺素能神经元中选择性消除 gp130 受体的动物进行了研究。这些突变小鼠的神经节中 VIP、甘丙肽和 PACAP 的 mRNA 水平没有显着变化,而缩胆囊素的增加与野生型小鼠一样大。数据表明,轴索切除术后 VIP、甘丙肽和 PACAP 的诱导完全依赖于 gp130 细胞因子,并且除了 LIF 之外还涉及第二种细胞因子。然而,轴索切除术后胆囊收缩素的增加不需要这些细胞因子的作用。
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. Prior to 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 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.
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