Leukemia Inhibitory Factor and Ciliary Neurotrophic Factor Cause Dendritic Retraction in Cultured Rat Sympathetic Neurons

Leukemia Inhibitory Factor and Ciliary Neurotrophic Factor Cause Dendritic Retraction in Cultured Rat Sympathetic Neurons
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DOI:
10.1523/jneurosci.19-06-02113.1999
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发表时间:
1999-03
期刊:
The Journal of Neuroscience
影响因子:
--
通讯作者:
Xin Guo;V. Chandrasekaran;P. Lein;P. Kaplan;D. Higgins
Xin Guo;V. Chandrasekaran;P. Lein;P. Kaplan;D. Higgins
中科院分区:
其他
文献类型:
--
作者:
Xin Guo;V. Chandrasekaran;P. Lein;P. Kaplan;D. Higgins

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树突回缩发生在发育中的大脑的许多区域中,也发生在神经损伤后。然而,调节这一重要退化过程的分子在很大程度上仍然未知。我们的数据表明,白血病抑制因子(LIF)和睫状神经营养因子(CNTF)引起交感神经元收缩树突在体外,最终导致在乔木的大小减少约80%。LIF诱导的树突状回缩表现出很大的特异性,因为它不伴随着细胞数量的变化,轴突生长的速度,或轴突细胞骨架元素的表达。gp 130的抗体阻断LIF和CNTF的作用,两种细胞因子均诱导stat 3的磷酸化和核转位。此外,向培养基中添加可溶性白细胞介素-6(IL-6)受体赋予IL-6引起树突消退的能力。这些数据表明,配体激活gp 130通路有能力深刻地改变神经元细胞的形状和极性,通过选择性地引起树突的收缩。
Dendritic retraction occurs in many regions of the developing brain and also after neural injury. However, the molecules that regulate this important regressive process remain largely unknown. Our data indicate that leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) cause sympathetic neurons to retract their dendrites in vitro, ultimately leading to an ∼80% reduction in the size of the arbor. The dendritic retraction induced by LIF exhibited substantial specificity because it was not accompanied by changes in cell number, in the rate of axonal growth, or in the expression of axonal cytoskeletal elements. An antibody to gp130 blocked the effects of LIF and CNTF, and both cytokines induced phosphorylation and nuclear translocation of stat3. Moreover, addition of soluble interleukin-6 (IL-6) receptor to the medium endowed IL-6 with the ability to cause dendritic regression. These data indicate that ligands activating the gp130 pathway have the ability to profoundly alter neuronal cell shape and polarity by selectively causing the retraction of dendrites.