Exposure to extremely low-frequency (50 Hz) electromagnetic fields enhances adult hippocampal neurogenesis in C57BL/6 mice
Exposure to extremely low-frequency (50 Hz) electromagnetic fields enhances adult hippocampal neurogenesis in C57BL/6 mice
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DOI：
10.1016/j.expneurol.2010.08.022
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发表时间：
2010-11-01
影响因子：
5.3
通讯作者：
Grassi, Claudio
中科院分区：
文献类型：
--
作者：
Cuccurazzu, Bruna;Leone, Lucia;Grassi, Claudio
在整个生命过程中，海马体不断产生新的神经元，因此海马体是成人大脑结构可塑性的主要部位。我们最近证明了极低频电磁场（ELFEFs）通过上调Ca(v)1通道活性促进体外神经干细胞的神经元分化。本研究的目的是确定50 hz /1 mT ELFEF刺激是否也会影响体内成年海马神经发生，如果是的话，确定这种作用的分子机制及其对突触可塑性的功能影响。ELFEF暴露（每天1至7小时，持续7天）显著增强成年小鼠齿状回（DG）的神经发生，这可以通过增加5-溴脱氧尿苷（BrdU）和双皮质素双重标记的细胞数量来证明。海马提取物定量RT-PCR分析显示，ELFEF暴露诱导的前神经元基因（Mash1、NeuroD2、Hes1）和编码Ca(v)1.2通道α (1C)亚基的基因转录显著增加。Western blot分析显示，NeuroD1、NeuroD2和Ca(v)1通道表达增加。免疫荧光实验显示，ELFEF刺激30天后，大约一半的新生未成熟神经元存活并成为成熟的齿状颗粒细胞（从它们对BrdU和NeuN的免疫反应性可以看出），并整合到DG的颗粒细胞层。电生理实验表明，新生的成熟神经元影响海马突触的可塑性，表现为长时程增强。我们的研究结果表明，ELFEF暴露可能是增加体内神经发生的有效工具，它们可能导致再生医学中新的治疗方法的发展。(C) 2010爱思唯尔公司版权所有。
Throughout life, new neurons are continuously generated in the hippocampus, which is therefore a major site of structural plasticity in the adult brain. We recently demonstrated that extremely low-frequency electromagnetic fields (ELFEFs) promote the neuronal differentiation of neural stem cells in vitro by up-regulating Ca(v)1-channel activity. The aim of the present study was to determine whether 50-Hz/1 mT ELFEF stimulation also affects adult hippocampal neurogenesis in vivo, and if so, to identify the molecular mechanisms underlying this action and its functional impact on synaptic plasticity. ELFEF exposure (1 to 7 h/day for 7 days) significantly enhanced neurogenesis in the dentate gyrus (DG) of adult mice, as documented by increased numbers of cells double-labeled for 5-bromo-deoxyuridine (BrdU) and doublecortin. Quantitative RT-PCR analysis of hippocampal extracts revealed significant ELFEF exposure-induced increases in the transcription of pro-neuronal genes (Mash1, NeuroD2, Hes1) and genes encoding Ca(v)1.2 channel alpha(1C) subunits. Increased expression of NeuroD1, NeuroD2 and Ca(v)1 channels was also documented by Western blot analysis. Immunofluorescence experiments showed that, 30 days after ELFEF stimulation, roughly half of the newly generated immature neurons had survived and become mature dentate granule cells (as shown by their immunoreactivity for both BrdU and NeuN) and were integrated into the granule cell layer of the DG. Electrophysiological experiments demonstrated that the new mature neurons influenced hippocampal synaptic plasticity, as reflected by increased long-term potentiation. Our findings show that ELFEF exposure can be an effective tool for increasing in vivo neurogenesis, and they could lead to the development of novel therapeutic approaches in regenerative medicine. (C) 2010 Elsevier Inc. All rights reserved.