Deficits in water maze performance and oxidative stress in the hippocampus and striatum induced by extremely low frequency magnetic field exposure.
ABSTRACT The exposures to extremely low frequency magnetic field (ELF-MF) in our environment have dramatically increased. Epidemiological studies suggest that there is a possible association between ELF-MF exposure and increased risks of cardiovascular disease, cancers and neurodegenerative disorders. Animal studies show that ELF-MF exposure may interfere with the activity of brain cells, generate behavioral and cognitive disturbances, and produce deficits in attention, perception and spatial learning. Although, many research efforts have been focused on the interaction between ELF-MF exposure and the central nervous system, the mechanism of interaction is still unknown. In this study, we examined the effects of ELF-MF exposure on learning in mice using two water maze tasks and on some parameters indicative of oxidative stress in the hippocampus and striatum. We found that ELF-MF exposure (1 mT, 50 Hz) induced serious oxidative stress in the hippocampus and striatum and impaired hippocampal-dependent spatial learning and striatum-dependent habit learning. This study provides evidence for the association between the impairment of learning and the oxidative stress in hippocampus and striatum induced by ELF-MF exposure.
[show abstract] [hide abstract]
ABSTRACT: Electrification in developed countries has progressively increased the mean level of extremely low-frequency electromagnetic fields (ELF-EMFs) to which populations are exposed; these humanmade fields are substantially above the naturally occurring ambient electric and magnetic fields of approximately 10(-4) Vm(-1) and approximately 10(-13) T, respectively. Several epidemiological studies have concluded that ELF-EMFs may be linked to an increased risk of cancer, particularly childhood leukemia. These observations have been reinforced by cellular studies reporting EMF-induced effects on biological systems, most notably on the activity of components of the pathways that regulate cell proliferation. However, the limited number of attempts to directly replicate these experimental findings have been almost uniformly unsuccessful, and no EMF-induced biological response has yet been replicated in independent laboratories. Many of the most well-defined effects have come from gene expression studies; several attempts have been made recently to repeat these key findings. This review analyses these studies and summarizes other reports of major cellular responses to EMFs and the published attempts at replication. The opening sections discuss quantitative aspects of exposure to EMFs and the incidence of cancers that have been correlated with such fields. The concluding section considers the problems that confront research in this area and suggests feasible strategies.The FASEB Journal 04/1998; 12(6):395-420. · 5.71 Impact Factor
Article: Radiofrequency radiation (900 MHz) induces Egr-1 gene expression and affects cell-cycle control in human neuroblastoma cells.[show abstract] [hide abstract]
ABSTRACT: Many environmental signals, including ionizing radiation and UV rays, induce activation of Egr-1 gene, thus affecting cell growth and apoptosis. The paucity and the controversial knowledge about the effect of electromagnetic fields (EMF) exposure of nerve cells prompted us to investigate the bioeffects of radiofrequency (RF) radiation on SH-SY5Y neuroblastoma cells. The effect of a modulated RF field of 900 MHz, generated by a wire patch cell (WPC) antenna exposure system on Egr-1 gene expression, was studied as a function of time. Short-term exposures induced a transient increase in Egr-1 mRNA level paralleled with activation of the MAPK subtypes ERK1/2 and SAPK/JNK. The effects of RF radiations on cell growth rate and apoptosis were also studied. Exposure to RF radiation had an anti-proliferative activity in SH-SY5Y cells with a significant effect observed at 24 h. RF radiation impaired cell cycle progression, reaching a significant G2-M arrest. In addition, the appearance of the sub-G1 peak, a hallmark of apoptosis, was highlighted after a 24-h exposure, together with a significant decrease in mRNA levels of Bcl-2 and survivin genes, both interfering with signaling between G2-M arrest and apoptosis. Our results provide evidence that exposure to a 900 MHz-modulated RF radiation affect both Egr-1 gene expression and cell regulatory functions, involving apoptosis inhibitors like Bcl-2 and survivin, thus providing important insights into a potentially broad mechanism for controlling in vitro cell viability.Journal of Cellular Physiology 01/2008; 213(3):759-67. · 3.87 Impact Factor
Article: A case-control study of occupational magnetic field exposure and Alzheimer's disease: results from the California Alzheimer's Disease Diagnosis and Treatment Centers.[show abstract] [hide abstract]
ABSTRACT: A few studies have investigated a possible relationship between Alzheimer's disease (AD) and occupations with extremely low frequency magnetic field (MF) exposure. The purpose of this study was to further evaluate this possible association in a large patient population with expert diagnoses. Subjects came from the 8 of the 9 California Alzheimer's Disease Diagnostic and Treatment Centers not previously used in an earlier study. Cases had probable or definite AD; controls primarily had a dementia-related problem other than vascular dementia (VaD) and some were not demented upon expert examination. Occupations were classified as having low, medium or high MF exposure, based upon previous research, replicating the exposure methodology used in our previous published studies. Occupational information was available for 98.6% of the 1527 cases and 98.5% of the 404 controls with age-at-initial examination known to be at least 65. Among cases, 2.1% and 5.4% had high and medium occupational MF exposure, respectively, while among controls the percentages were 0.8% and 3.0%. In univariate analyses, the odds ratio (OR) for subjects with medium or high MF exposures combined was 2.1 (p < 0.01), while for high exposure alone the OR was 2.9 (p < 0.08). Two models were used in multivariate analyses, with gender, stroke, and either age-at-onset or age-at-initial examination as covariates. The ORs for MF exposure varied little between the two models: 2.2 (p < 0.02) and 1.9 (p < 0.03) for medium or high exposure; 2.7 (p < 0.11) and 3.2 (p < 0.12) for high exposure. OR estimates for females were higher than for males, but not significantly higher. There were no material differences between the ORs resulting from univariate and multivariate analyses. Elevated occupational MF exposure was associated with an increased risk of AD. Based on previous published studies, the results likely pertain to the general population.BMC Neurology 01/2007; 7:13. · 2.17 Impact Factor
Deficits in Water Maze Performance and Oxidative Stress
in the Hippocampus and Striatum Induced by Extremely
Low Frequency Magnetic Field Exposure
Yonghua Cui1., Zhiqiang Ge1., Joshua Dominic Rizak2., Chao Zhai1, Zhu Zhou1, Songjie Gong1, Yi Che1*
1Medical College of Soochow University, Suzhou, People’s Republic of China, 2Laboratory of Primate Neuroscience Research, Key Laboratory of Animal Models, Kunming
Institute of Zoology, Chinese Academy of Science, Kunming, People’s Republic of China
The exposures to extremely low frequency magnetic field (ELF-MF) in our environment have dramatically increased.
Epidemiological studies suggest that there is a possible association between ELF-MF exposure and increased risks of
cardiovascular disease, cancers and neurodegenerative disorders. Animal studies show that ELF-MF exposure may interfere
with the activity of brain cells, generate behavioral and cognitive disturbances, and produce deficits in attention, perception
and spatial learning. Although, many research efforts have been focused on the interaction between ELF-MF exposure and
the central nervous system, the mechanism of interaction is still unknown. In this study, we examined the effects of ELF-MF
exposure on learning in mice using two water maze tasks and on some parameters indicative of oxidative stress in the
hippocampus and striatum. We found that ELF-MF exposure (1 mT, 50 Hz) induced serious oxidative stress in the
hippocampus and striatum and impaired hippocampal-dependent spatial learning and striatum-dependent habit learning.
This study provides evidence for the association between the impairment of learning and the oxidative stress in
hippocampus and striatum induced by ELF-MF exposure.
Citation: Cui Y, Ge Z, Rizak JD, Zhai C, Zhou Z, et al. (2012) Deficits in Water Maze Performance and Oxidative Stress in the Hippocampus and Striatum Induced by
Extremely Low Frequency Magnetic Field Exposure. PLoS ONE 7(5): e32196. doi:10.1371/journal.pone.0032196
Editor: Paul A Adlard, Mental Health Research Institute and the University of Melbourne, Australia
Received July 16, 2011; Accepted January 24, 2012; Published May 3, 2012
Copyright: ? 2012 Cui et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by National Basic Research Program of China, Chinese National Science Foundation (31172089). The funders had no role in
study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: firstname.lastname@example.org
. These authors contributed equally to this work.
The exposures to extremely low frequency magnetic field (ELF-
MF) in our environment have dramatically increased, which
include both occupational exposure and general exposure to
sources, such as power lines, household electrical wiring and
medical devices . Epidemiological studies suggest that there is
a possible association between ELF-MF exposure and increased
risks of cardiovascular disease, cancers and neurodegenerative
disorders [2–6]. Additionally, animal studies have shown that
ELF-MF exposure (50 Hz, 1 mT) generated behavioral and
cognitive disturbances, and produced deficits in attention,
perception and spatial learning in rats . Our research group
has also demonstrated that ELF-MF exposure (50 Hz, 1 mT)
induced significant impairments in detour learning and one-trial
passive avoidance learning in chicks [8,9].
Although, many research efforts have been focused on the
interaction between ELF-MF exposure and the central nervous
system, the mechanism of interaction is still unknown [10,11].
Some reports suggested that ELF-MF exposure may affect
biological systems by increasing the life span and concentration
of reactive oxygen species (ROS) and free radicals [12,13,14]. Lai
and Singh reported that ELF-MF exposure (60 Hz, 0.01 mT)
caused DNA damage in rat brain cells with the involvement of
oxygen free radical processes , Ravera et al. reported that ELF-
MF exposure (75 Hz, 0.74 mT) decreased the activity of different
membrane-anchored enzymes , Amara et al. reported that
subchronic static magnetic fields exposure (128 mT) induced
oxidative stress in the rat hippocampus and frontal cortex ,
and Jelenkovic et al. reported that ELF-MF exposure (50 Hz,
0.5 mT) was harmful to the brain, especially to the basal forebrain
and frontal cortex due to development of lipid peroxidation .
It is well known that the increases of free radicals lead to
oxidative damage in major cell macromolecules such as proteins,
lipids, and nucleic acids. The brain tissues, especially the
hippocampal and striatum neurons, are considered particularly
vulnerable to oxidative damage because of their high lipid content,
enrichment in mitochondria, comparatively high oxygen utiliza-
tion, and modest antioxidant defences .
Previous studies have emphasized the effects of ELF-MF
exposure on learning behavior and on the antioxidant status of
various tissues and organs. However, no reports have been found
in the literature to provide direct evidence that the impairment of
learning induced by ELF-MF exposure involves oxidative stress.
Therefore, it seemed reasonable to verify the hypothesis that ELF-
MF exposure induces oxidative stress in some brain areas,
damages the brain structure and function, and then impairs
learning ability. The present investigation was designed to evaluate
the effects of chronic ELF-MF exposure on habit learning which is
dependent on striatum [20,21], and on spatial learning which is
PLoS ONE | www.plosone.org1May 2012 | Volume 7 | Issue 5 | e32196
dependent on hippocampus [20,22], as well as evaluate some
parameters indicative of oxidative stress in these two structures.
We believe that this study may provide more evidence for the
hypothesis that the impairment of learning induced by ELF-MF
exposure involves oxidative stress.
Materials and Methods
All experiments were conducted during the light phase, and in
accordance with procedures approved by Animal Experimental
Committee, Soochow University, and with the National Institutes
of Health Guidelines for the Care and Use of Laboratory Animals
Seventy-two adult male C57BL/6 mice weighing 19,21 g at
the beginning of the experiment were housed in pairs in plexiglas
cages with food and water ad libitum throughout the experimental
period. The mice were maintained in a climate-controlled colony
room at 24uCon a 12/12 h reverse light/dark cycle. All mice were
allowed 1 week adaptation to the housing rooms prior to the
initiation of treatment. After adapting, mice received ELF-MF
exposure 4 hours/day for 12 consecutive weeks. Mice were
randomly assigned to three groups (n=24 animals/group). Group
I received sham ELF-MF exposure 4 hours/day. Sham-exposed
mice were placed in a similar, but non-energized apparatus.
Group II received 50 Hz, 1 mT ELF-MF exposure 4 hours/day.
Group III received 50 Hz, 0.1 mT ELF-MF exposure 4 hours/
After the exposure period, all mice were evaluated in an open-
field test and with a water-maze learning and memory task.
Following these evaluations, the animals were slightly anesthetized
and sacrificed by decapitation. Their brains were rapidly removed,
and the hippocampus and striatum were carefully dissected out
according to a mouse brain atlas with a previously described
Magnetic Field Exposure System
As previously described , the electromagnetic field was
generated by a single coil of four layers, each having 250 turns.
Each layer was wrapped horizontally above the previous layer
around a 70 cm640 cm643 cm plastic frame. The coil was
connected to a waveform generator for modulating the frequency
and intensity of the electromagnetic field. By varying the input
current to the coil, the flux density of electromagnetic fields in the
exposure area can be adjusted from ambient levels to the
maximum coil-designed electromagnetic field strength of 14 mT.
The exposure area (60 cm630 cm643 cm) was inside the coil.
During exposure,mice were
(50 cm625 cm, with 25 cm high walls) which was mechanically
isolated from the magnet and rested on a freestanding wood. The
mice were free to move about the box ad libitum. The variation of
the electromagnetic fields in the plastic box was 64.5% of the
mean and was determined by measurement with a Gaussmeter.
placed ina plastic box
Open Field Test
In order to determine whether ELF-MF exposure produced
ataxia or motor impairments in the mice, locomotor activity was
monitored in an open field enclosed in a black Plexiglas square box
(40640630 cm). The open field tests were conducted after the 12
weeks of ELF-MF exposure. On the test day, mice were placed in
the center of the black Plexiglas square box (40640630 cm) for
a 5 min. Mice activity was recorded with a video camera that was
connected to a computer.
Water Maze Test
The mice were submitted to two versions of the water maze task
after the open field test. The water maze consisted of a round tank,
110 cm in diameter and 30 cm deep, filled with water. The water
temperature was maintained at 25uC. Several visual cues were
placed on the walls of the laboratory. The latency to reach the
escape platform was recorded with a video camera that was
connected to a computer.
Thirty-six mice (n=12/group) were submitted to a spatial
reference memory version of the water maze. This consisted of 4
training days, four consecutive trials per day, during which the
animals were randomly left in the tank facing the wall, and allowed
to swim freely to a transparent escape platform (8 cm in diameter)
submersed 2 cm under the water surface, placed in the center of
one of the four imaginary quadrants of the tank. The escape
platform position was maintained constant throughout all 4
training days. After the animal escaped to the platform it was
allowed to remain on it for 30 s and was then removed from the
tank for 30 s before being placed in the next random initial
position. If the animal did not find the platform during a period of
60 s it was gently guided to it .
The other thirty-six mice (n=12/group) were submitted to a cue
version of the water maze similar to the previous experimental
procedure, except that the position of the escape platform was
cued by a yellow ping-pong ball attached to the top of the platform
and floating above the water. Additionally, the position of the
platform was always changed in this version of the water maze for
each trial of the day. This memory task was a model of habit
Determination of Oxidative Stress
Mouse hippocampus and striatum were homogenized in
10:1 (vol/wt) ice-cold PBS. A quantity of the homogenate was
used to determine the activities of catalase (CAT), glutathione
peroxidase (GSH-PX), total antioxidant capability (T-AOC) and
the concentration of malondialdehyde (MDA) in the hippocampus
and striatum samples according to the manufacturer’s protocol
(Nanjing Jiancheng Bioengineering Institute, Nanjing, China).
These methods are described briefly below.
CAT is responsible for the detoxification of H2O2, a precursor
for intracellular free radicals . The activity of CAT in the
samples was measured by the decrease in the H2O2concentration.
The H2O2 decomposition reaction catalysed by catalase was
stopped by adding ammonium molybdate. The remaining H2O2
combined with ammonium molybdate to form a yellow com-
pound, which absorbed maximally at 405 nm. One unit of
catalase activity was defined as 1 mmol of decomposed H2O2in
one milligram of tissue for one minute and expressed as units per
The T-AOC is a useful index for the capacity of tissue samples
to modulate the damage associated with enhanced production of
free radicals . A spectrometric method was applied to evaluate
the T-AOC. In the reaction mixture, ferric ions were reduced by
antioxidant reducing agents and a blue complex Fe2+–TPTZ
(2,4,6-tri(2-pyridyl)-s-triazine) was produced. One unit of T-AOC
was equal to 0.01 increases in absorbance of the reaction mixture
at 520 nm per milligram protein per minute under 37uC
incubation. The T-AOC activities were expressed as units per
GSH-PX is responsible for breaking down peroxides . The
activity of GSH-PX was measured by measuring the rate of
Oxidative Stress Induced by Electromagnetic Field
PLoS ONE | www.plosone.org2May 2012 | Volume 7 | Issue 5 | e32196
(2GSH+H2O2RGSSG+2H2O) as catalyzed by GSH-PX present
in the sample. The activity was measured with the addition of
glutathione reductase and NADPH. Glutathione reductase con-
verts oxidized glutathione (GSSG) to the reduced form, while
oxidizing NADPH to NADP. The rate of GSSG formation was
subsequently measured by following the decrease in absorbance of
the reaction mixture at 340 nm as NADPH was converted to
NADP. A GSH-PX unit was defined as the enzyme activity
required to convert 1 nmol of NADPH to NADP per mg tissue
protein. The GSH-PX activity was expressed as units per mg
MDA is one of the most frequently used indicators of lipid
peroxidation . The thiobarbituric acid reaction (TBAR)
method was used to determine the MDA. The method was used
to obtain a spectrophotometric measurement of the color
produced during the reaction of TBA with MDA at 535 nm.
MDA content was expressed as nmol/mg protein.
Protein concentrations were determined according to the Lowry
Statistical analysis was performed using SPSS software. All
results were expressed as mean 6 standard error of the mean.
Differences between groups in body weight, oxidative stress levels
and the distance in open field were analyzed by one-way repeated
measures analysis of variance (ANOVA) followed by a post hoc
LSD test. Escape latencies in water maze were analyzed by two-
way repeated measures ANOVA using treatment as the between-
subjects factor and session day as the repeated measure.
Differences were considered to be statistically significant when
Body Weight and Locomotion
During the treatment, animals were all in the growth state.
There was no significant difference in weight gain across the three
groups [F(2,33)=0.271, p=0.764]. The effect of ELF-MF
exposure on general locomotor activity of the mice was examined
in an open field test and the ELF-MF exposure did not cause
significant differences in horizontal locomotion [F(2,33)=0.767,
p=0.516]. This finding suggests that magnetic field exposure did
not produce ataxia or motor impairments in the mice.
ELF-MF Exposure Induced Oxidative Stress in the
Hippocampus and Striatum
The levels of CAT, GSH-PX, T-AOC and MDA in mice
hippocampus and striatum were determined in this study. ELF-
MF exposure (0.1 mT) for 12 weeks did not result in the
development of oxidative stress in mice hippocampus or striatum.
However, ELF-MF exposure for 12 weeks (1 mT) resulted in the
development of oxidative stress in mice hippocampus and
striatum. The levels of MDA in mice hippocampus and striatum,
parameters of oxidative stress, were significantly increased in the
1 mT ELF-MF exposure group compared with the other two
F(2,33)=23.148, p,0.001]. The levels of CAT, GSH-PX, and
T-AOC in hippocampus [CAT: F(2,33)=7.765, p=0.002; GSH-
p,0.001] and striatum [CAT: F(2,33)=16.31, p,0.001; GSH-
PX: F(2,33)=11.89, p,0.001; T-AOC: F(2,33)=4.37, p=0.021]
were significantly declined in 1 mT ELF-MF exposure group
compared with the other two groups (Fig 1, Table 1).
ELF-MF Exposure Induced Learning Deficit in the Water
The effect of ELF-MF exposure on the scores of the mice in the
spatial reference memory version of the water maze is presented in
Fig. 2. Two-way repeated measures ANOVA indicated a signifi-
cant effect of group [F(2, 33)=9.43, P=0.014], a significant effect
of training day [F(3, 99)=70.6, P,0.001] and a significant
interaction between group and training day [F(6, 99)=20.8,
P,0.001]. The effect of ELF-MF exposure on the scores of the
mice in the cue memory version of the water maze is presented in
Fig. 2. Two-way repeated measures ANOVA indicated a signifi-
cant effect of group [F(2, 33)=16.08, P=0.004], a significant
effect of training day [F(3, 99)=268, P,0.001] and a significant
interaction between group and training day [F(6, 99)=2.923,
P=0.01]. The mean escape latency of the mice improved
throughout the training days indicating that the mice were able
to learn the two versions of the task. However, the ELF-MF
exposure (1 mT) group took longer to find the platform compared
with the other two groups (p,0.001). Where as, no significant
deficit was observed in the ELF-MF exposure (0.1 mT) mice
Figure 1. The Antioxidatant Status in Mice Hippocampus and
Striatum. After extremely low frequency magnetic field (ELF-MF)
exposure for consecutive 12 weeks, the antioxidatant status in mice
hippocampus and striatum was impaired by ELF-MF exposure (1 mT)
but not by ELF-MF exposure (0.1 mT). Values represent means6SEM.
N=12. * indicates p,0.05.
Oxidative Stress Induced by Electromagnetic Field
PLoS ONE | www.plosone.org3May 2012 | Volume 7 | Issue 5 | e32196
There are many factors that increase ROS concentration in
cells, animals and humans. A magnetic field can alter the energy
levels and spin orientation of electrons and, as a consequence,
increase the activity, concentration and lifetime of free radicals
[12,13,14]. Oxidative stress results from an imbalance between the
generation of free radicals and endogenous protective mechan-
isms. These protective mechanisms include enzymes that specif-
ically degrade potential ROS precursors, such as CAT that
degrades hydrogen-peroxide, and GSH-PX that degrades hydro-
gen-peroxide in a reaction where reduced glutathione is converted
to oxidized glutathione .
The present study demonstrated that, in general, exposure to an
ELF-MF decreased the activity of antioxidant enzymes and
increased the MDA level in two neuronal tissues; the hippocampus
and striatum, respectively. The decrease in antioxidant enzyme
activity levels might be interpreted as a decrease in protein
expression levels in response to the ELF-MF exposure or
potentially as the indirect inhibition of the enzymes by their
binding with oxidative molecules produced during the ELF-MF
exposure. Nonetheless, the GPX and CAT activity decreases may
lead to hydrogen-peroxide accumulation, which is favorable to the
peroxidation of lipids in tissues .
Additionally, the findings of this study show that ELF-MF
exposure (50 Hz, 1 mT) impaired the learning of mice in the two
versions of the water maze: the spatial reference memory version
of the water maze was a declarative memory model which was
dependent on the hippocampus [20,21], and the cue version of the
water maze task was a habit learning model which was dependent
on the striatum [20,22]. This study provided direct evidence for
the association between the impairment of learning induced by
ELF-MF exposure (50 Hz, 1 mT) and oxidative stress in these two
brain regions associated with learning and memory.
ROS can activate signal transduction pathways, cause DNA
damage, and result in the modification of gene expression.
Moreover, the overproduction of oxygen free radicals can give
rise to functional and morphological disturbances in the cell
through oxidative stress [12,18,19]. We speculate that the
oxidative stress induced by ELF-MF exposure (50 Hz, 1 mT)
may damage the structure and function of hippocampus and
striatum in the mice, and therefore impair their ability to generate
declarative memory and habit learning.
Yet, the relationship between ELF-MF exposure, oxidative
stress and learning impairments is not clearly defined, despite
many studies attempting to investigate ELF-MF. For example,
Mostafa et al. reported that exposure to ELF-MF (50 Hz,
0.2 mT, 24 per day for 1, 2 or 4 weeks) was associated with
impairment in discrimination between familiar and novel objects,
where as Sienkiewicz et al. found no effect of ELF-MF exposure
(50 Hz, 75 mT, 45 min, once only) on object discrimination
[28,29]. Lee et al. reported that ELF-MF exposure (60 Hz, 1 mT)
had no influence on the transformation activities of stress factors
such as reactive oxygen species . Our previous results also
complicate the issue. We have shown that exposure to ELF-MF
(50 Hz,1 mT, 50 min per day) had no effect on response latency
Table 1. The activities of CAT, GSH-PX, T-AOC and the concentration of MDA.
GroupCAT(U/mg protein)GSH-PX(U/mg protein) T-AOC(U/mg protein)MDA(nmol/mg protein)
Hippocampus control 21.2161.2631.2260.931.6560.083.8360.19
Hippocampus 1 mT 14.2860.84* 20.1564.65*0.5960.22* 9.5760.26*
Hippocampus 0.1 mT19.3261.89 30.0761.241.2960.16 4.3760.32
Striatum control23.7260.94 39.8161.99 1.8260.105.1060.21
Striatum 1 mT14.4561.89*22.6861.99* 1.3560.19*9.3860.31*
Striatum 0.1 mT21.0961.18 32.6363.581.7460.055.9160.51
Figure 2. Effect of Electromagnetic Fields Exposure on Two
Versions of Water Maze Task. The data represent the latency time
to escape to a submersed platform during 4 training days, with four
consecutive trials per day. Mice exposed to extremely low frequency
magnetic fields (1 mT) took longer to find the platform in the two
versions of the water maze compared with the other two groups
(p,0.001). No significant deficit in the two versions of the task was
observed in the ELF-MF (0.1 mT) exposed mice (p.0.05). Values
represent means6SEM. N=12. * indicates p,0.05.
Oxidative Stress Induced by Electromagnetic Field
PLoS ONE | www.plosone.org4May 2012 | Volume 7 | Issue 5 | e32196
of detour learning, but that exposure to ELF-MF (50 Hz, 1 mT,
20 hours per day) significantly delayed detour learning .
Nonetheless, the inconsistencies found in the results of these
studies may have been due to the differences in the duration of
ELF-MF exposure between these studies. Furthermore, the
present study showed that the mice of the ELF-MF exposure
(1 mT, 4 hours per day) group needed more time to learn the
water maze task than the mice of the other two groups and that
the development of learning and memory was delayed by ELF-
MF (1 mT, 4 hours per day) chronic exposure, where as ELF-
MF (0.1 mT, 4 hours per day) chronic exposure did not have an
effect on learning or on oxidative stress. All told, the present
results, along with the listed previous studies, suggest that the
biological effects of ELF-MF exposure depend on the dosage and
duration of ELF-MF exposure.
It is also interesting to note that despite the growing body of
evidence that links ELF-MF to neurological disfunction and the
worrying reports these deleterious effects might have, a small
number of studies have suggested beneficial effects of low magnetic
or ELF-MF on human health under certain circumstances
Nonethelss, our results do suggest that there may be a negative
effect of chronic exposure to ELF-MF (50 Hz, 1 mT, 4 hours per
day) on learning and memory, and that this negative effect is
associated with oxidative stress. Although, a detailed inquiry into
the factors that gave rise to the learning impairment observed here
was beyond the scope of the data collected, we believe that the
effects of ELF-MF exposure may be complex and subtle and that
precise relationship between ELF-MF strength and biological
response needs further study.
Conceived and designed the experiments: Y. Che ZG CZ ZZ SG Y. Cui.
Performed the experiments: Y. Cui CZ ZZ SG. Analyzed the data: Y. Che
ZG Y. Cui. Contributed reagents/materials/analysis tools: Y. Cui ZG CZ
ZZ SG Y. Che. Wrote the paper: Y. Che ZG Y. Cui JR.
1.Lacy-Hulbert A, Metcalfe JC, Hesketh R (1998) Biological responses to
electromagnetic fields. FASEB J 12: 395–420.
Buttiglione M, Roca L, Montemurno E, Vitiello F, Capozzi V, et al. (2007)
Radiofrequency radiation (900 MHz) induces Egr-1 gene expression and affects
cell-cycle control in human neuroblastoma cells. J Cell Physiol 213: 759–767.
Davanipour Z, Tseng CC, Lee PJ, Sobel E (2007) A case-control study of
occupational magnetic field exposure and Alzheimer’s disease: Results from the
California Alzheimer’s disease diagnosis and treatment centers. BMC Neurol 9:
Davanipour Z, Sobel E (2009) Long-term exposure to magnetic fields and the
risks of Alzheimer’s disease and breast cancer: Further biological research
Review Article. Pathophysiology 16: 149–156.
Hakansson N, Gustavsson P, Sastre A, Floderus B (2003) Occupational exposure
to extremely low-frequency magnetic fields and mortality from cardiovascular
disease. Am J Epidemiol 158: 534–542.
Loomis DP, Savitz DA (1990) Mortality from brain cancer and leukemia among
electrical workers. Br J Ind Med 47: 633–638.
Trimmel M, Schweiger E (1998) Effects of an ELF-MF (50 Hz, 1 mT)
electromagnetic field (EMF) on concentration in visual attention, perception and
memory including effects of EMF sensitivity. Toxicology Letters 96–97:
Che Y, Sun HY, Cui YH, Zhou D, Ma Y (2007) 50 Hz magnetic field effects on
the performance of a detour learning task by chicks. Brain Research Bulltin 74:
Sun H, Che Y, Liu X, Zhou D, Miao Y, et al. (2010) Effects of prenatal exposure
to a 50-Hz magnetic field on one-trial passive avoidance learning in 1-day-old
chicks. Bioelectromagnetics 311: 50–5.
10. Ahmed Z, Wieraszko A (2008) The mechanism of magnetic field-induced
increase of excitability in hippocampal neurons. Brain Research 1221: 30–40.
11. Maaroufi K, Had-Aissouni L, Melon C, Sakly M, Abdelmelek H, et al. (2009)
Effects of prolonged iron overload and low frequency electromagnetic exposure
on spatial learning and memory in the young rat. Neurobiology of Learning and
Memory 92: 345–355.
12. Hulbert AL, Metcalfe J, Hesketh R (1998) Biological response to electromagnetic
fields. FASEB J 12: 395–420.
13. Prato FS, Kavaliers M, Carson JJ (1996) Behavioural evidence that magnetic
field effects in the land snail, Cepaea nemoralis, might not depend on magnetite
or induced electric currents. Bioelectromagnetics 17: 123–130.
14. Roy S, Noda Y, Eckert V, Traber MG, Mori A, et al. (1995) The phorbol 12-
myristate 13-acetate (PMA)-induced oxidative burst in rat peritoneal neutrophils
is increased by a 0.1 mT (60 Hz) magnetic field. FEBS Lett 376: 164–166.
15. Lai H, Singh NP (2004) Magnetic-field-induced DNA strand breaks in brain
cells of the rat. Environ Health Perspect 112: 689–694.
16. Ravera S, Pepe IM, Calzia D, Morelli A, Panfoli I (2011) Extremely low-
frequency electromagnetic fields affect lipid-linked Carbonic anhydrase.
Electromagn Biol Med. 30: 67–73.
17. Amara S, Douki T, Garel C, Favier A, Sakly M, et al. (2009) Effects of static
magnetic field exposure on antioxidative enzymes activity and DNA in rat brain.
Gen Physiol Biophys 28: 260–265.
18. Jelenkovic A, Janac B, Pesic V, Jovanovic DM, Vasiljevic I, et al. (2006) Effects
of extremely low-frequency magnetic field in the brain of rats. Brain Research
Bulletin 68: 355–360.
19. Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now?
J Neurochem 97: 1634–1658.
20. Miyoshi E, Wietzikoski S, Camplessei M, Silveira R, Takahashi RN, et al. (2002)
Impaired learning in a spatial working memory version and in a cued version of
the water maze in rats with MPTP-induced mesencephalic dopaminergic
lesions. Brain Res Bull 58: 41–47.
21. Packard MG, McGaugh JL (1992) Double dissociation of fornix and caudate
nucleus lesions on acquisition of two water maze tasks: Further evidence for
multiple memory systems. Behav Neurosci 106: 439–446.
22. Morris RGM, Garrud P, Rawlins JNP, Okeefe J (1982) Place navigation
impaired in rats with hippocampal lesions. Nature 297: 681–683.
23. Prasad K, Tarasewicz E, Mathew J, Strickland PO, Buckley B, et al. (2009)
Toxicokinetics and toxicodynamics of paraquat accumulation in mouse brain.
Experimental Neurology 215: 358–367.
24. Mittler R (2002) Oxidative stress, antioxidants and stress tolerance. Trends Plant
Sci. 7: 405–410.
25. Lissi E, Pascual C, Castillo MD (1992) Luminol luminescence induced by 2,20-
azo-bis(2-amidinopropane) thermolysis. Free Radic Res Commun.
26. Ljubuncic P, Tanne Z, Bomzon A (2000) Evidence of a systemic phenomenon
for oxidative stress in cholestatic liver disease. Gut 47: 710–716.
27. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement
with the Folin phenol reagent. J Biol Chem 193: 265–275.
28. Mostafa RM, Mostafa YM, Ennaceur A (2002) Effects of exposure to extremely
low-frequency magnetic field of 2 G intensity on memory and corticosterone
level in rats. Physiol Behav 765: 89–595.
29. Sienkiewicz ZJ, Bartram R, Haylock RG, Saunders RD (2001) Single, brief
exposure to a 50 Hz magnetic field does not affect the performance of an object
recognition task in adult mice. Bioelectromagnetics 22: 19–26.
30. Lee HJ, Jin YB, Lee JS, Choi JI, Lee JW, et al. (2011) Combined effects of 60 Hz
electromagnetic field exposure with various stress factors on cellular trans-
formation in NIH3T3 cells. Bioelectromagnetics. 2011 [Epub ahead of print].
31. Keck ME, Welt T, Post A, Muller MB, Toschi N, et al. (2001) Neuroendocrine
and behavioral effects of repetitive transcranial magnetic stimulation in
a psychopathological animal model are suggestive of antidepressant-like effects.
Neuropsychopharmacology 24: 337–349.
32. Reyes-Guerrero G, Vazquez-Garcia M, Elias-Vinas D, Donatti-Albarran OA,
Guevara-Guzman R (2006) Effects of 17 b-estradiol and extremely low-
frequency electromagnetic fields on social recognition memory in female rats:
A possible interaction? Brain Research 1095: 131–138.
33. Lopuch S (2009) A magnetic field effect on learning in male golden hamsters.
Behavioural Processes 81: 133–135.
Oxidative Stress Induced by Electromagnetic Field
PLoS ONE | www.plosone.org5 May 2012 | Volume 7 | Issue 5 | e32196