Trophic and proliferative effects of Shh on motor neurons in embryonic spinal cord culture from wildtype and G93A SOD1 mice.

Trophic and proliferative effects of Shh on motor neurons in embryonic spinal cord culture from wildtype and G93A SOD1 mice.
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DOI:
10.1186/1471-2202-14-119
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发表时间:
2013-10-11
期刊:
影响因子:
2.4
通讯作者:
Turnbull J
Turnbull J
中科院分区:
医学4区
文献类型:
--
作者:
Ma X;Turnbull P;Peterson R;Turnbull J

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发育中的形态发生素音刺猬(Shh)可能继续在支持终末分化的运动神经元中发挥营养作用,这与运动神经元疾病具有潜在的相关性。此外,它可能支持内源干细胞沿着运动神经元谱系的增殖和分化。因此,我们在源自野生型或 G93A SOD1 小鼠(肌萎缩侧索硬化症小鼠模型)的胚胎脊髓细胞培养物中检查了补充 Shh 或 Shh 拮抗剂的营养和增殖作用。在源自 G93A SOD1 和 WT 小鼠的原代培养物中,Shh 支持存活并刺激运动神经元的生长、神经突生长和神经球形成。 Shh 增加了纤毛运动神经元的百分比,尤其是在 G93A SOD1 培养物中。与对照组,特别是环巴明处理的 G93A SOD1 和 WT 小鼠的培养物相比,Shh 处理的培养物显示出神经元增殖增加。此外,Shh 增强了 WT 培养物中运动神经元前体的细胞存活和分化。 Shh 对运动神经元具有神经营养作用,并且在 WT 和 mSOD1 G93A 体外培养物中具有促有丝分裂作用。
The developmental morphogen sonic hedgehog (Shh) may continue to play a trophic role in the support of terminally-differentiated motor neurons, of potential relevance to motor neuron disease. In addition, it may support the proliferation and differentiation of endogenous stem cells along motor neuronal lineages. As such, we have examined the trophic and proliferative effects of Shh supplementation or Shh antagonism in embryonic spinal cord cell cultures derived from wildtype or G93A SOD1 mice, a mouse model of amyotrophic lateral sclerosis. Shh supported survival, and stimulated growth of motor neurons, neurite outgrowth, and neurosphere formation in primary culture derived from both G93A SOD1 and WT mice. Shh increased the percentage of ciliated motor neurons, especially in G93A SOD1 culture. Shh-treated cultures showed increased neuronal proliferation compared to controls and especially cyclopamine treated cultures, from G93A SOD1 and WT mice. Moreover, Shh enhanced cell survival and differentiation of motor neuron precursors in WT culture. Shh is neurotrophic to motor neurons and has mitogenic effects in WT and mSOD1 G93A culture in vitro.
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