Abstract
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 Ca2+ 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 Ca2+ 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 Ca2+-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.
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Abbreviations
- ADAM10:
-
A disintegrin and metalloproteinase
- AMPA:
-
Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
- CREB:
-
Cyclic AMP-responsive element-binding protein
- DAPI:
-
4-6-diamidino-2-phenylindole-dihydrochloride
- EGFR:
-
Epidermal growth factor receptor
- ELF MF:
-
Extremely low frequency magnetic field
- hNPCs:
-
Human neural progenitor cells
- mT:
-
MilliTesla
- NMDA:
-
N-methyl-d-aspartate
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Funding
A. Ozgun was supported within the framework of European Molecular Biology Organization Short Term Fellowships, ASTF 7502. This work was partially supported by TUBITAK Projects under Grant No. 117Z864, Bogazici University Research Fund by Grant Number 6701. A.J. Salgado and A. Marote acknowledge the financial support from: Prémios Santa Casa Neurociências–Prize Melo e Castro for Spinal Cord Injury Research (MC-04/17); Portuguese Foundation for Science and Technology Pre–Doctoral fellowship to A. Marote PDE/BDE/113598/2015 and IF Development Grant to A. J. Salgado. This work is funded by national funds through FCT under the scope of grant reference TUBITAK/0007/2014. This article has been developed under the scope of the projects NORTE-01-0145-FEDER-000023, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038 and POCI-01-0145-FEDER-029206.
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António Salgado and Bora Garipcan share senior authorship.
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Özgün, A., Marote, A., Behie, L.A. et al. Extremely low frequency magnetic field induces human neuronal differentiation through NMDA receptor activation. J Neural Transm 126, 1281–1290 (2019). https://doi.org/10.1007/s00702-019-02045-5
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DOI: https://doi.org/10.1007/s00702-019-02045-5