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生长激素/胰岛素样生长因子1轴在神经发生中的作用。

Role of the growth hormone/insulin-like growth factor 1 axis in neurogenesis.

作者信息

Åberg David

出版信息

Endocr Dev. 2010;17:63-76. doi: 10.1159/000262529. Epub 2009 Nov 24.

Abstract

The growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis is not only involved in brain growth, development and myelination, but also in brain plasticity as indexed by neurogenesis. This may have links to various cognitive effects of GH and IGF-1. GH and IGF-1 affect the genesis of neurons, astrocytes, endothelial cells and oligodendrocytes. Specifically, IGF-1 increases progenitor cell proliferation and numbers of new neurons, oligodendrocytes, and blood vessels in the dentate gyrus of the hippocampus. In the adult cerebral cortex IGF-1 only affects oligodendrogenesis. Recently, GH therapy has also been shown to induce cell genesis in the adult brain. The profile of effects by GH therapy may be somewhat different than that of IGF-1. In addition, GH secretagogues (GHS) also have neuroprotective and cell regenerative effects per se in the brain. Finally, transgenic disruptions in GH signaling pathways affect neuron and astrocyte cell numbers during development and during adulthood. Altogether, data suggest that both exogenous and endogenous GH and/or IGF-1 may be used as agents to enhance cell genesis and neurogenesis in the adult brain. Theoretically these substances could be used to enhance recovery after brain injuries. However, further experiments with specific animal models for brain injuries are needed before clinical trials can be started.

摘要

生长激素/胰岛素样生长因子1(GH/IGF-1)轴不仅参与大脑的生长、发育和髓鞘形成,还与以神经发生为指标的大脑可塑性有关。这可能与GH和IGF-1的各种认知效应存在联系。GH和IGF-1影响神经元、星形胶质细胞、内皮细胞和少突胶质细胞的生成。具体而言,IGF-1可增加海马齿状回中祖细胞的增殖以及新神经元、少突胶质细胞和血管的数量。在成人大脑皮质中,IGF-1仅影响少突胶质细胞生成。最近,生长激素疗法也已被证明可诱导成人大脑中的细胞生成。生长激素疗法的效应模式可能与IGF-1有所不同。此外,生长激素促分泌素(GHS)本身在大脑中也具有神经保护和细胞再生作用。最后,GH信号通路中的转基因破坏会影响发育期间和成年期的神经元和星形胶质细胞数量。总之,数据表明外源性和内源性GH和/或IGF-1都可作为增强成人大脑中细胞生成和神经发生的药物。从理论上讲,这些物质可用于促进脑损伤后的恢复。然而,在开始临床试验之前,需要对特定的脑损伤动物模型进行进一步实验。

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