Magnesium Elevation Promotes Neuronal Differentiation While Suppressing Glial Differentiation of Primary Cultured Adult Mouse Neural Progenitor Cells through ERK/CREB Activation.
Magnesium Elevation Promotes Neuronal Differentiation While Suppressing Glial Differentiation of Primary Cultured Adult Mouse Neural Progenitor Cells through ERK/CREB Activation.
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DOI：
10.3389/fnins.2017.00087
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发表时间：
2017
影响因子：
4.3
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Liao W;Jiang M;Li M;Jin C;Xiao S;Fan S;Fang W;Zheng Y;Liu J
本研究旨在探讨镁水平升高对体外成体神经祖细胞（aNPCs）命运的影响及其机制。成年神经发生，即从神经前体生成功能性神经元，发生于哺乳动物一生中有限的解剖区域。镁是哺乳动物体内含量第四丰富的离子，其在大脑中的升高已被证明可以增强记忆和突触的可塑性。然而，镁对神经发生过程中至关重要的aNPCs命运决定的影响尚不清楚。从成年C57/BL6小鼠齿状回分离的NPCs在含不同镁浓度（0.6、0.8和1.0 mM）和细胞外信号调节激酶（ERK）抑制剂PD0325901的培养基中诱导分化。用免疫荧光法测定分化为神经元和神经胶质细胞的细胞比例。采用实时定量聚合酶链反应和Western blot法检测β-III微管蛋白（Tuj1）和胶质原纤维酸性蛋白（GFAP）的表达。Western blot检测ERK和cAMP反应元件结合蛋白（CREB）的激活，以揭示其潜在机制。镁升高使tju1阳性细胞比例升高，gfap阳性细胞比例降低。Tuj1表达上调，GFAP表达下调。此外，镁升高可增强ERK和CREB的激活。PD0325901以剂量依赖性的方式逆转了这些效应。镁升高促进神经分化，同时抑制胶质细胞分化，可能是通过erk诱导的CREB激活。
This study aimed to explore the influence of magnesium elevation on fate determination of adult neural progenitor cells (aNPCs) and the underlying mechanism in vitro. Adult neurogenesis, which is the generation of functional neurons from neural precursors, occurs throughout life in restricted anatomical regions in mammals. Magnesium is the fourth most abundant ion in mammals, and its elevation in the brain has been shown to enhance memory and synaptic plasticity in vivo. However, the effects of magnesium on fate determination of aNPCs, which are vital processes in neurogenesis, remain unknown. NPCs isolated from the dentate gyrus of adult C57/BL6 mice were induced to differentiate in a medium with varying magnesium concentrations (0.6, 0.8, and 1.0 mM) and extracellular signal-regulated kinase (ERK) inhibitor PD0325901. The proportion of cells that differentiated into neurons and glial cells was evaluated using immunofluorescence. Quantitative real-time polymerase chain reaction and Western blot methods were used to determine the expression of β-III tubulin (Tuj1) and glial fibrillary acidic protein (GFAP). The activation of ERK and cAMP response element-binding protein (CREB) was examined by Western blot to reveal the underlying mechanism. Magnesium elevation increased the proportion of Tju1-positive cells and decreased the proportion of GFAP-positive cells. Also, the expression of Tuj1 was upregulated, whereas the expression of GFAP was downregulated. Moreover, magnesium elevation enhanced the activation of both ERK and CREB. Treatment with PD0325901 reversed these effects in a dose-dependent manner. Magnesium elevation promoted neural differentiation while suppressing glial cell differentiation, possibly via ERK-induced CREB activation.