Insulin-like growth factor-I as a promoting factor for cerebellar Purkinje cell development
Insulin-like growth factor-I as a promoting factor for cerebellar Purkinje cell development
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DOI：
10.1046/j.1460-9568.2003.02640.x
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发表时间：
2003-05-01
影响因子：
3.4
通讯作者：
Kano, M
中科院分区：
文献类型：
--
作者：
Fukudome, Y;Tabata, T;Kano, M
在哺乳动物中枢神经系统中，多肽激素胰岛素样生长因子-I(IGF-I)是在一定的神经元亚群中合成的，并被认为是一种局部神经营养因子。出生后IGF-I和IGF受体(IGFR1)在小脑皮质及其相关脑区的表达增加，提示发育中的小脑浦肯野细胞(PC)可能是IGF-I的一个重要靶点。然而，人们对IGF-I如何影响PC开发知之甚少。在这里，我们解决了这个问题，使用了来自围产期小鼠的小脑神经元培养的简化环境。外源性应用生理浓度(10 Nm)的IGF-I可显著促进PC的树突状生长和存活。相比之下，IGF-I仅轻微促进PC的体细胞生长，对其电生理兴奋性的成熟影响不大。与胰岛素密切相关的激素胰岛素的促进作用弱于IGF-I。胰岛素样生长因子-I似乎至少与胰岛素样生长因子受体结合，并上调信号通路，涉及磷脂酰肌醇3-激酶(PI3-K)、丝裂原活化蛋白激酶(MAPK)、p38K(P38K)和一个未知的信号分子(S)。这些信号通路可能以不同的方式与PC发展的各个方面相耦合，这可能解释了IGF-I在这些方面的作用不同。这些发现表明，IGF-I是PC发育的促进因子，特别是出生后存活和树突生长。
In the mammalian CNS, the peptide hormone insulin-like growth factor-I (IGF-I) is synthesized in a certain subset of neurons and, it has been suggested, serves as a local neurotrophic factor. A postnatal increase in the expression of IGF-I and the type-1 IGF receptors (IGFR1) in the cerebellar cortex and its related brain regions indicates that developing cerebellar Purkinje cells (PC) may be an important target of IGF-I. However, little is known about how IGF-I influences PC development. Here we addressed this question, using a reduced environment of cerebellar neuron culture derived from perinatal mice. IGF-I exogenously applied at a physiological concentration (10 nm) greatly promoted the dendritic growth and survival of the PCs. By contrast, IGF-I only slightly promoted the somatic growth and little affected the maturation of the electrophysiological excitability of the PCs. The closely related hormone insulin had weaker promoting effects than did IGF-I. IGF-I appeared to at least bind to IGFR1 and to up-regulate the signalling pathways involving the phosphoinositide 3-kinase (PI3-K), mitogen-activated protein kinase (MAPK), p38 kinase (p38K), and an unknown signalling molecule(s). These signalling pathways may be coupled to the individual aspects of PC development in different manners and this may explain the difference in effects of IGF-I among these aspects. These findings suggest that IGF-I serves as a promoting factor for PC development, particularly postnatal survival and dendritic growth.