Medical/biological study (experimental study)

Fifty hertz extremely low-frequency magnetic field exposure elicits redox and trophic response in rat-cortical neurons. med./bio.

By: Di Loreto S, Falone S, Caracciolo V, Sebastiani P, D'Alessandro A, Mirabilio A, Zimmitti V, Amicarelli F

Published in: J Cell Physiol 2009; 219 (2): 334-343

Aim of study (acc. to author)

To study the changes in the redox status and the antioxidant and detoxificant enzymatic defence protection, as well as the variations in growth factor and cytokine expression profile induced in rat cortical neurons by the exposure to two different extremely low frequency magnetic field intensities (0.1 and 1 mT) during cell maturation.

Background/further details

The levels of malondialdehyde were also investigated in order to evaluate whether this extremely low frequency magnetic field-based experimental model is able to cause evident oxidative damages to high polyunsaturated fatty acids-rich neuronal cell membranes (typically for cortical neurons).
The study was performed with cortical neurons because these cells are particularly susceptible to oxidative stressors and are also highly dependent on the specific factors and proteins governing neuronal development, activity and survival.

Endpoint

redox status, antioxidant and detoxificant enzymatic defence protection, growth factor and cytokine expression profile

Exposure

Exposure	Parameters
Exposure 1: 50 Hz Exposure duration: continuous for 7 days	magnetic flux density: 0.1 mT (reference level recommended by the European Community for general public exposure) magnetic flux density: 1 mT (10-fold the reference level recommended by the European Community for occupational exposure)

Exposure 1

Main characteristics

Frequency	50 Hz
Type	magnetic field
Waveform	sinusoidal
Exposure duration	continuous for 7 days

Exposure setup

Exposure source	solenoid
Setup	solenoids with forced air circulation
Sham exposure	A sham exposure was conducted.

Parameters

Measurand	Value	Type	Method	Mass	Remarks
magnetic flux density	0.1 mT	-	measured	-	reference level recommended by the European Community for general public exposure
magnetic flux density	1 mT	-	measured	-	10-fold the reference level recommended by the European Community for occupational exposure

Reference articles

Piacentini R et al. (2008): Extremely low-frequency electromagnetic fields promote in vitro neurogenesis via upregulation of Ca(v)1-channel activity.
Lisi A et al. (2005): Exposure to 50 Hz electromagnetic radiation promote early maturation and differentiation in newborn rat cerebellar granule neurons.

Exposed system:

intact cell/cell culture

Methods Endpoint/measurement parameters/methodology

molecular biosynthesis: growth factor and cytokine gene expression and protein expression (NGF, BDNF, interleukin-1beta, tyrosine kinase A (receptor for NGF), tyrosine kinase B (BDNF receptor); RT-PCR, Western blot, ELISA (for interleukin-1beta)); formation of reactive oxygen species (flow cytometry and fluorescence microscopy)
cell function: antioxidant and detoxificant enzymatic defence protection (enzyme activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase and g-glutamylcysteine synthetase (spectrophotometry)); lipid peroxidation (MDA level; thiobarbituric acid-based assay)
cell viability/cell division/proliferation: cell viability (tetrazolium-based assay), apoptosis (apoptotic DNA fragmentation; cell death detection ELISA kit)
redox status (reduced glutathione levels; flow cytometry)

Investigated system:

isolated bio./chem. substance
DNA/RNA
intact cell/cell culture
cell extracts, suspensions and lysates

Time of investigation:

after exposure

Main outcome of study (acc. to author)

The data showed that extremely low frequency magnetic fields affected positively the cell viability and concomitantly reduced the levels of apoptotic cell death in rat neuronal primary cultures, with no significant effects on the main anti-oxidative defences. Linear regression analysis indicated a positive correlation between the levels of reduced glutathione and reactive oxygen species in 1 mT magnetic field-exposed cells.
This adaptive response was probably mediated by a redox-related mechanism involving reduced glutathione scavenging action and by the enhancement of neurotrophic support.

Study character:

medical/biological study
experimental study
full/main study

Study funded by

Italian Space Agency (Agenzia Spaziale Italiana, ASI), Italy

Zeng Y et al. (2017): Effects of Single and Repeated Exposure to a 50-Hz 2-mT Electromagnetic Field on Primary Cultured Hippocampal Neurons.
Reale M et al. (2016): Effect of environmental extremely low-frequency electromagnetic fields exposure on inflammatory mediators and serotonin metabolism in a human neuroblastoma cell line.
Mahmoudinasab H et al. (2016): Effects of extremely low-frequency electromagnetic field on expression levels of some antioxidant genes in human MCF-7 cells.
Fan W et al. (2015): 50 Hz electromagnetic field exposure promotes proliferation and cytokine production of bone marrow mesenchymal stem cells.
Lewicka M et al. (2015): The impact of electromagnetic radiation of different parameters on platelet oxygen metabolism - in vitro studies.
Reale M et al. (2014): Neuronal cellular responses to extremely low frequency electromagnetic field exposure: implications regarding oxidative stress and neurodegeneration.
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.
Raus S et al. (2013): Response of hippocampal neurons and glial cells to alternating magnetic field in gerbils submitted to global cerebral ischemia.
Martinez-Samano J et al. (2012): Effect of acute extremely low frequency electromagnetic field exposure on the antioxidant status and lipid levels in rat brain.
Cui Y et al. (2012): Deficits in water maze performance and oxidative stress in the hippocampus and striatum induced by extremely low frequency magnetic field exposure.
Ciejka E et al. (2011): Effects of extremely low frequency magnetic field on oxidative balance in brain of rats.
Chu LY et al. (2011): Extremely low frequency magnetic field induces oxidative stress in mouse cerebellum.
Sulpizio M et al. (2011): Molecular basis underlying the biological effects elicited by extremely low-frequency magnetic field (ELF-MF) on neuroblastoma cells.
Frahm J et al. (2010): Exposure to ELF magnetic fields modulate redox related protein expression in mouse macrophages.
Polaniak R et al. (2010): Influence of an Extremely Low Frequency Magnetic Field (ELF-EMF) on Antioxidative Vitamin E Properties in AT478 Murine Squamous Cell Carcinoma Culture In Vitro.
Morabito C et al. (2010): Modulation of redox status and calcium handling by extremely low frequency electromagnetic fields in C2C12 muscle cells: A real-time, single-cell approach.
Farina M et al. (2010): ELF-EMFs induced effects on cell lines: controlling ELF generation in laboratory.
Henrykowska G et al. (2009): The effect of 50 Hz magnetic field of different shape on oxygen metabolism in blood platelets: in vitro studies.
Hashish AH et al. (2008): Assessment of biological changes of continuous whole body exposure to static magnetic field and extremely low frequency electromagnetic fields in mice.
Erdal N et al. (2008): Effects of Long-term Exposure of Extremely Low Frequency Magnetic Field on Oxidative/Nitrosative Stress in Rat Liver.
Falone S et al. (2008): Chronic exposure to 50Hz magnetic fields causes a significant weakening of antioxidant defence systems in aged rat brain.
Falone S et al. (2007): Fifty hertz extremely low-frequency electromagnetic field causes changes in redox and differentiative status in neuroblastoma cells.