Institute of Biomedical Engineering, Bogazici University, Istanbul, Turkey.
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
J Neural Transm (Vienna). 2019 Oct;126(10):1281-1290. doi: 10.1007/s00702-019-02045-5. Epub 2019 Jul 17.
Magnetic fields with different frequency and intensity parameters exhibit a wide range of effects on different biological models. Extremely low frequency magnetic field (ELF MF) exposure is known to augment or even initiate neuronal differentiation in several in vitro and in vivo models. This effect holds potential for clinical translation into treatment of neurodegenerative conditions such as autism, Parkinson's disease and dementia by promoting neurogenesis, non-invasively. However, the lack of information on underlying mechanisms hinders further investigation into this phenomenon. Here, we examine involvement of glutamatergic Ca channel, N-methyl-D-aspartate (NMDA) receptors in the process of human neuronal differentiation under ELF MF exposure. We show that human neural progenitor cells (hNPCs) differentiate more efficiently under ELF MF exposure in vitro, as demonstrated by the abundance of neuronal markers. Furthermore, they exhibit higher intracellular Ca levels as evidenced by c-fos expression and more elongated mature neurites. We were able to neutralize these effects by blocking NMDA receptors with memantine. As a result, we hypothesize that the effects of ELF MF exposure on neuronal differentiation originate from the effects on NMDA receptors, which sequentially triggers Ca-dependent cascades that lead to differentiation. Our findings identify NMDA receptors as a new key player in this field that will aid further research in the pursuit of effect mechanisms of ELF MFs.
磁场具有不同的频率和强度参数,对不同的生物模型表现出广泛的影响。已知极低频率磁场(ELF MF)暴露可增强甚至启动几种体外和体内模型中的神经元分化。这种效应有可能通过促进神经发生,非侵入性地将临床转化为治疗自闭症、帕金森病和痴呆等神经退行性疾病。然而,缺乏对潜在机制的信息阻碍了对这一现象的进一步研究。在这里,我们研究了谷氨酸能 Ca 通道、N-甲基-D-天冬氨酸(NMDA)受体在 ELF MF 暴露下人类神经元分化过程中的作用。我们表明,人神经祖细胞(hNPC)在体外 ELF MF 暴露下更有效地分化,这表现为神经元标记物的丰度增加。此外,它们表现出更高的细胞内 Ca 水平,如 c-fos 表达和更长的成熟神经突所示。我们能够通过用美金刚阻断 NMDA 受体来中和这些效应。因此,我们假设 ELF MF 暴露对神经元分化的影响源于对 NMDA 受体的影响,这依次触发 Ca 依赖性级联反应,导致分化。我们的发现将 NMDA 受体确定为该领域的一个新的关键参与者,这将有助于进一步研究 ELF MF 的作用机制。
J Neural Transm (Vienna). 2019-7-17
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