Guo X, Chandrasekaran V, Lein P, Kaplan P L, Higgins D
Department of Pharmacology and Toxicology, State University of New York, Buffalo, New York 14214, USA.
J Neurosci. 1999 Mar 15;19(6):2113-21. doi: 10.1523/JNEUROSCI.19-06-02113.1999.
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 approximately 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.
树突回缩发生在发育中大脑的许多区域，也发生在神经损伤后。然而，调节这一重要退行性过程的分子在很大程度上仍不为人知。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）在体外可导致交感神经元的树突回缩，最终使树突分支大小减少约80%。LIF诱导的树突回缩表现出显著的特异性，因为它并未伴随细胞数量、轴突生长速率或轴突细胞骨架成分表达的变化。针对gp130的抗体可阻断LIF和CNTF的作用，且这两种细胞因子均可诱导stat3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）受体可赋予IL-6引起树突退化的能力。这些数据表明，激活gp130途径的配体能够通过选择性地引起树突回缩而深刻改变神经元细胞的形状和极性。
