Leukemia inhibitory factor determines the growth status of injured adult sensory neurons

Leukemia inhibitory factor determines the growth status of injured adult sensory neurons
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DOI:
10.1523/jneurosci.21-18-07161.2001
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发表时间:
2001-09-15
影响因子:
5.3
通讯作者:
Thompson, SWN
Thompson, SWN
中科院分区:
医学1区
文献类型:
--
作者:
Cafferty, WBJ;Gardiner, NJ;Thompson, SWN

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对成年哺乳动物感觉神经元的条件性损伤增强其再生潜力。在这里,我们表明,白血病抑制因子(LIF)是一个基本组成部分的条件反射。体内条件性损伤显著增加LIF+/+小鼠体外感觉神经元的内在生长能力。这种条件作用在来自LIF-/-小鼠的感觉神经元中显著减弱。在LIF-/-小鼠中,通过添加外源性LIF在体外挽救了生长增强,并且该作用被人LIF-05(一种LIF受体拮抗剂)阻断。此外,我们证明,LIF促进延长,但不树枝状突起生长在体外,是所需的正常再生损伤的成年感觉神经元在体内。LIF还对体内神经损伤后的肽能感觉神经元具有功能保护作用。我们的研究结果表明,损伤的感觉神经元的内在生长状态的改变依赖于,至少部分地,在LIF。
Conditioning injury to adult mammalian sensory neurons enhances their regeneration potential. Here we show that leukemia inhibitory factor (LIF) is a fundamental component of the conditioning response. Conditioning injury in vivo significantly increases the intrinsic growth capacity of sensory neurons in vitro from LIF+/+ mice. This conditioning effect is significantly blunted in sensory neurons from LIF-/- mice. Enhanced growth is rescued in vitro in LIF-/- mice by the addition of exogenous LIF, and the effect blocked by human LIF-05, an LIF receptor antagonist. Furthermore, we demonstrate that LIF promotes elongating but not arborizing neurite outgrowth in vitro and is required for normal regeneration of injured adult sensory neurons in vivo. LIF is also functionally protective to peptidergic sensory neurons after nerve damage in vivo. Our results indicate that the alteration in intrinsic growth status of injured sensory neurons depends, at least in part, on LIF.