Medical/biological study (experimental study)

Extremely low-frequency electromagnetic fields enhance the proliferation and differentiation of neural progenitor cells cultured from ischemic brains med./bio.

By: Cheng Y, Dai Y, Zhu X, Xu H, Cai P, Xia R, Mao L, Zhao BQ, Fan W

Published in: NeuroReport 2015; 26 (15): 896-902

Aim of study (acc. to author)

The effects of exposure of neural progenitor cells from adult ischemic and embryonic mice brains to a 50 Hz magnetic field on proliferation and neural differentiation should be investigated.

Background/further details

Neural progenitor cells play a crucial role in regeneration after brain injuries and may therefore be of therapeutic use.
Cells were divided into the following groups: 1) magnetic field exposure of embryo-derived cells, 2) control group for embryo-derived cells, 3) magnetic field exposure of adult-derived cells, 4) co-exposure of adult-derived cells to magnetic field and Wortmannin, 5) control group for adult-derived cells. Wortmannin is a specific inhibitor of the protein kinase B, whose signal pathway was investigated as a possible underlying mechanism of action.

Endpoint

cell viability/cell division/proliferation: proliferation and neural differentiation of neural progenitor cells

Exposure

- 50 Hz
- 50/60 Hz
- magnetic field

Exposure	Parameters
Exposure 1: 50 Hz Exposure duration: continuous for up to 7 days	magnetic flux density: 0.4 mT (uniformity of field ± 0.012 mT)

Exposure 1

Main characteristics

Frequency	50 Hz
Type	magnetic field
Exposure duration	continuous for up to 7 days

Exposure setup

Exposure source	solenoid
Chamber	incubator
Setup	the solenoid was positioned into a water-jacketed temperature- and atmosphere-regulated incubator (37 ± 0.4°C, 5% CO₂)
Additional info	control samples were placed in another identical incubator

Parameters

Measurand	Value	Type	Method	Mass	Remarks
magnetic flux density	0.4 mT	-	measured	-	uniformity of field ± 0.012 mT

Reference articles

He YL et al. (2013): Exposure to Extremely Low-Frequency Electromagnetic Fields Modulates Na(+) Currents in Rat Cerebellar Granule Cells through Increase of AA/PGE(2) and EP Receptor-Mediated cAMP/PKA Pathway

Exposed system:

intact cell/cell culture
neural progenitor cells from the brain of mice embryos and ischemic brain of adult mice (C57BL/6J)

Methods Endpoint/measurement parameters/methodology

cell function: markers of signal pathways (only with adult-derived cells after 16 hours: protein expression of protein kinase B (Akt), phosphorylated protein kinase B, phosphorylated ERK, phosphorylated JNK and phosphorylated mitogen activated protein kinase (p38); Western blot)
cell viability/cell division/proliferation: cell proliferation (after 4-32 hours in embryo-derived cells and after 16 h in adult-derived cells: bromodeoxyuridine incorporation); cell differentiation (after 16 hours and 7 days in embryo-derived cells and after 7 days in adult-derived cells: detection of neurons, astrocytes and oligodendrocytes via the respective specific markers TUJ-1, GFAP and O4) (immunohistochemistry, microscopy)

Investigated system:

isolated bio./chem. substance
intact cell/cell culture
cell lysates

Time of investigation:

during exposure
after exposure

Main outcome of study (acc. to author)

Exposure to the magnetic field significantly increased the cell proliferation and the amount of differentiated neurons in both embryo-derived (group 1) and adult-derived (group 3) cells compared to their respective control group (group 2 or 5). Astrocyte differentiation did not show any significant differences between the exposure and control groups. The oligodendrocyte differentiation could not be analyzed due to a lack of detectable markers.
The amount of phosphorylated protein kinase B was significantly increased in exposed adult-derived cells (group 3) in comparison to the respective control group. Co-exposure to magnetic field and Wortmannin, however, decreased the amount of phosphorylated protein kinase B and reduced the cell proliferation significantly compared to the exposure group. All other signal pathway markers did not show any significant differences between the groups.
The authors conclude that exposure of neural progenitor cells from adult ischemic and embryonic mice brains to a 50 Hz magnetic field might enhance proliferation and neuronal differentiation. The effects of the magnetic field might be mediated via the protein kinase B pathway.

Study character:

medical/biological study
experimental study
full/main study

Study funded by

Ministry of Education, China
Ministry of Science and Technology (MOST), China
National Basic Research Program (Program 973), China
National Key Drug Discovery Projects, China
National Natural Science Foundation (NSFC), China
Natural Science Foundation of Shanghai, China
Shanghai Municipal Education Commission, China
Shanghai Municipal Science and Technology Commission, China

Bai W et al. (2021): Comparison of effects of high- and low-frequency electromagnetic fields on proliferation and differentiation of neural stem cells
Su L et al. (2017): The effects of 50 Hz magnetic field exposure on DNA damage and cellular functions in various neurogenic cells
Ma Q et al. (2016): Extremely low-frequency electromagnetic fields promote in vitro neuronal differentiation and neurite outgrowth of embryonic neural stem cells via up-regulating TRPC1
Urnukhsaikhan E et al. (2016): Pulsed electromagnetic fields promote survival and neuronal differentiation of human BM-MSCs
Duong CN et al. (2016): Exposure to electromagnetic field attenuates oxygen-glucose deprivation-induced microglial cell death by reducing intracellular Ca(2+) and ROS
de Groot MW et al. (2016): In vitro developmental neurotoxicity following chronic exposure to 50 Hz extremely low frequency electromagnetic fields (ELF-EMF) in primary rat cortical cultures
Li Y et al. (2014): Pulsed electromagnetic field enhances brain-derived neurotrophic factor expression through L-type voltage-gated calcium channel- and Erk-dependent signaling pathways in neonatal rat dorsal root ganglion neurons
Choi YK et al. (2014): Stimulation of neural differentiation in human bone marrow mesenchymal stem cells by extremely low-frequency electromagnetic fields incorporated with MNPs
Seong Y et al. (2014): Egr1 mediated the neuronal differentiation induced by extremely low-frequency electromagnetic fields
Ma Q et al. (2014): Extremely low-frequency electromagnetic fields affect transcript levels of neuronal differentiation-related genes in embryonic neural stem cells
Leone L et al. (2014): Epigenetic modulation of adult hippocampal neurogenesis by extremely low-frequency electromagnetic fields
Podda MV et al. (2014): Extremely low-frequency electromagnetic fields enhance the survival of newborn neurons in the mouse hippocampus
Morabito C et al. (2010): Effects of Acute and Chronic Low Frequency Electromagnetic Field Exposure on PC12 Cells during Neuronal Differentiation
Marcantonio P et al. (2010): Synergic effect of retinoic acid and extremely low frequency magnetic field exposure on human neuroblastoma cell line BE(2)C
Piacentini R et al. (2008): Extremely low-frequency electromagnetic fields promote in vitro neurogenesis via upregulation of Ca(v)1-channel activity
Pozzi D et al. (2007): Effect of 50 Hz magnetic field exposure on neuroblastoma morphology
Pirozzoli MC et al. (2003): Effects of 50 Hz electromagnetic field exposure on apoptosis and differentiation in a neuroblastoma cell line
McFarlane EH et al. (2000): Changes in neurite outgrowth but not in cell division induced by low EMF exposure: influence of field strength and culture conditions on responses in rat PC12 pheochromocytoma cells