Insulin-like growth factor 1 (IGF1) and its active peptide (1-3)IGF1 enhance the expression of synaptic markers in neuronal circuits through different cellular mechanisms

Insulin-like growth factor 1 (IGF1) and its active peptide (1-3)IGF1 enhance the expression of synaptic markers in neuronal circuits through different cellular mechanisms
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DOI:
10.1016/j.neulet.2012.05.029
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发表时间:
2012-06-27
影响因子:
2.5
通讯作者:
Tropea, Daniela
Tropea, Daniela
中科院分区:
医学4区
文献类型:
--
作者:
Corvin, Aiden P.;Molinos, Ines;Tropea, Daniela

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胰岛素样生长因子-1(IGF 1)及其活性肽(1-3)IGF 1调节大脑生长和可塑性,是治疗脑部疾病的候选分子。IGF 1的N-末端部分被天然切割以产生三肽(1-3)IGF 1(甘氨酸-脯氨酸-谷氨酸)。IGF 1和(1-3)IGF已被提议作为神经病理学的治疗,但它们对神经细胞的作用尚未被直接比较。在这项研究中,我们研究了IGF 1和(1-3)IGF 1在原代皮层培养中的作用,并测量了细胞内通路和突触功能标记物的表达水平。我们发现,这两种治疗激活IGF 1受体和增强突触标记物的表达,然而,它们激活不同的细胞内途径。此外,(1-3)IGF 1施用增加内源性IGF 1的表达,表明两种分子之间的直接相互作用。结果表明,这两种分子通过激活不同的细胞机制增加突触蛋白的表达。(c)2012爱思唯尔爱尔兰有限公司保留所有权利。
Insulin-like growth factor-1 (IGF1) and its active peptide (1-3)IGF1 modulate brain growth and plasticity and are candidate molecules for treatment of brain disorders. IGF1 N-terminal portion is naturally cleaved to generate the tri-peptide (1-3)IGF1 (glycine-praline-glutamate). IGF1 and (1-3)IGF have been proposed as treatment for neuropathologies, yet their effect on nerve cells has not been directly compared. In this study we examine the effects of IGF1 and (1-3)IGF1 in primary cortical cultures and measure the expression levels of markers for intracellular pathways and synaptic function. We find that both treatments activate the IGF1 receptor and enhance the expression of synaptic markers, however, they activate different intracellular pathways. Furthermore, (1-3)IGF1 administration increases the expression of endogenous IGF1, suggesting a direct interaction between the two molecules. The results show that the two molecules increase the expression of synaptic proteins through activating different cellular mechanisms. (c) 2012 Elsevier Ireland Ltd. All rights reserved.