Possible Effects of Radiofrequency Electromagnetic Field Exposure on Central Nervous System
There is a constant geomagnetic field on the surface of the planet as solar wind generated from the sun meets with the inside of the earth. Therefore, all life on Earth is always living in the presence of an electromagnetic field (EMF) (Hollenbach and Herndon, 2001). With the development of science and technology, artificial electromagnetic waves have been generated on Earth, and the German physicist Heinrich Hertz experimentally discovered electromagnetic radiation and confirmed the existence of the EMF in the ecosystem.
With the progress of science and technology, many electronic devices have been invented and used, therefore, we have easily been exposed to the created artificial electromagnetic waves in our daily life. Especially, explosive use of various electronic devices in modern society has inevitably led to increase continuously the chances of electromagnetic wave exposure. The development of wireless communication technologies, such as computers and smartphones, have become a necessity for modern people. As a consequence, all living things on Earth are experiencing environmental changes and are being exposed to artificial electromagnetic waves which have not been experienced before.
The effect of electromagnetic waves on living creatures has been controversial due to studies with contradicting results. However, in 2011, since the World Health Organization’s International Agency for Research on Cancer (IARC) designated mobile phone RF-EMFs as Group 2B, that is, possibly carcinogenic to humans, the social anxiety about electromagnetic exposure has increased (Baan et al., 2011). Considering the fact that most people, including young children, use mobile phones in Korea, the possibility of exposure to a considerable amount of electromagnetic waves exists all around us, therefore social interest in the impact on RF-EMF exposure has been greatly increased (Langer et al., 2017).
There are many controversies regarding RF-EMF exposure, but many of the studies have focused on cancer (Morgan et al., 2015), genetic damage (Kim et al., 2008; Ruediger, 2009), neurological disease (Jiang et al., 2016; Kim et al., 2017b), reproductive disorders (Falzone et al., 2011; Altun et al., 2018), immune dysfunction (Kazemi et al., 2015; Ohtani et al., 2015), kidney damage (Kuybulu et al., 2016; Türedi et al., 2017), as well as electromagnetic hypersensitivity (Gruber et al., 2018), and cognitive effects (Son et al., 2018). However, the possible biological effects of exposure to RF-EMF have not yet been proven and there are insufficient data on the biological hazards to provide a clear answer to possible health risks. Thus, the vague fear for the many unknown effects of RF-EMF exposure is expressed as ungrounded negative effects not only to the scientific community but also to the general public. In addition to this, scientific data published by various researchers have been contradictory in their outcome. In particular, detailed information regarding the mechanism of biological effect by RF-EMFs has not yet been elucidated clearly. Recent studies show that RF-EMFs emitted by cellular phones are absorbed into the brain, to a degree, that can affect neuronal activity (Kleinlogel et al., 2008; Jeong et al., 2015; Jiang et al., 2016). In addition, the thermal effects of RF-EMFs suggest the possibility of affecting neuronal activity by temperature generated by mobile phones (Wainwright, 2000; Wyde et al., 2018). Therefore, there is a need for scientifically proven information on the effects of increasing exposure to RF-EMFs on nerve cells, including neurodevelopment, function and cognitive functions (Calvente et al., 2016; Birks et al., 2017). However, many studies on the possible influence of electromagnetic waves on neurons have recently been conducted with great interest, but there are conflicting results according to experimental conditions and there is still much to be studied to gain a basic understanding.
EFFECTS OF EMF ON LEARNING AND MEMORY
It has been hypothesized that various neurological effects may arise as a result of RF-EMF exposure due to the proximity of the cranial nervous system during cellular phone use. These neurological effects include headache (Frey, 1998), changes in sleep habits (Wagner et al., 1998; Danker-Hopfe et al., 2016), changes in electroencephalogram (Mann et al., 1998; Schmid et al., 2012), and changes in blood pressure (Braune et al., 1998) but there are many inconsistent results. Neurological cognitive disorders, such as headache, tremor, dizziness, loss of memory, loss of concentration and sleep disturbance due to RF-EMF have also been reported by several epidemiological studies (Kolodynski and Kolodynska, 1996; Santini et al., 2002; Hutter et al., 2006; Abdel-Rassoul et al., 2007). The exposure levels of RF-EMF, commonly encountered in public environments have been found to be nondetrimental level to human (Repacholi et al., 2012), however with respect to the amount of exposure to RF-EMFs on the cranial nervous systems, a significant amount of research has focused on rodent behavioral disorders, particularly learning and memory deficits, after RF-EMF exposure under various conditions.
The radial maze and Morris water maze test showed that learning and memory functions were reduced in rats exposed to 2,450 MHz EMF (Lai et al., 1994; Wang and Lai, 2000), but no changes of working memory were observed in the radial maze test following whole body exposure for 45 minutes for 10 days at 2,450 MHz, 0.6 W/kg SAR (Cassel et al., 2004; Cobb et al., 2004) and in the Y-maze, Morris water maze, and novel object recognition memory test after exposed to 1950 MHz electromagnetic fields (SAR 5 W/kg, 2 h/day, 5 days/week) for 3 months (Son et al., 2016). Recognition memory was studied using the object recognition test (Mortazavi et al., 2014) using a head-only exposed mouse (900 MHz GSM, 1 and 3.5 W/kg SAR). In this study, there was no effect on learning and memory at low SAR levels, but at high SAR levels, only some of the exploration activities were changed (Dubreuil et al., 2002, 2003). Although exposure to RF-EMFs could affect cognitive function such as spatial learning and memory loss in both humans (Hossmann and Hermann, 2003; Preece et al., 1999) and in animals (Yamaguchi et al., 2003), direct evidence for the effects of RF-EMFs on these functions remains unclear (Ammari et al., 2008). The hippocampus is involved in spatial memory and learning processes (Morris et al., 1982; Moser et al., 1998) and low-intensity RF-EMFs at 700 MHz can alter electrical activity in hippocampal slices of the rat brain (Tattersall et al., 2001). Similarly, exposure to 1,800 MHz (15 min per day for 8 days, SAR 2.40 W/kg) has been reported to reduce excitatory synaptic activity of cultured hippocampal neurons (Xu et al., 2006). Although the water maze test results showed increased behavioral performance, there were no changes in spatial memory performances shown by both the open field or the plus maze tests, as well as in acoustic startle experiments in juvenile rats exposed to a 900 MHz for 5 weeks (2 hours per day, 5 days per week, SAR 3 W/kg) (Kumlin et al., 2007).
Recently, with regard to the effect of RF-EMFs on cognitive function, it has been found that exposure induced the improvement in cognitive behavior of triple transgenic mice (3xTg-AD), that have a cognitive impairment such as in human Alzheimer’s disease (Banaceur et al., 2013). This experiment was performed with a Wi-Fi type, 2.40 GHz RF signal for 2 hours a day for 1 month at 1.60 W/kg SAR. Experimental results suggest that exposure of RF-EMF can lead to effective memory recovery in cognitive impairment in an experimental animal with loss of cognitive function caused by Alzheimer’s disease (Banaceur et al., 2013). Despite numerous studies, it remains unclear if RF-EMF exposure is a risk for cognitive function, including memory. However, transgenic Alzheimer’s mice with long-term RF-EMF exposure for more than 8 months have been reported to improve cognitive abilities (Arendash et al., 2010; Son et al., 2018). These series of experimental results suggest that exposure to RF-EMFs can improve memory in Alzheimer’s disease, which is based on reduced response time, less anxiety, but no effect on exercise activity, body weight or body temperature (Arendash et al., 2010; Banaceur et al., 2013).
EFFECTS OF EMF ON MYELIN SHEATH
The Schwann cell, a glial cell, forms a myelin sheath, enclosing an axon of a peripheral neuron, which play a role as an insulator of axon fiber. The myelin sheaths form a spiral-like structure surrounding axons and are essential for the survival of neurons (Bhatheja and Field, 2006). Because it plays a key role in maintaining the survival of nerve cells, damage to the myelin sheath leads to demyelinating diseases such as chronic inflammatory demyelinate polyneuropathy. Demyelination could induce conduction velocity reduction, action potential dispersion and conduction block, and eventually cause axonal damage. Thus, the state of the myelin sheath is very important in the development and function of a healthy nervous system (Redmayne and Johansson, 2014). Exposure to RF-EMFs can cause significant structural changes in the myelin protein, affecting the proteins associated with myelinogenesis, leading to symptoms of electro-hypersensitivity (Redmayne and Johansson, 2014; Kim et al., 2017b). The inflammatory mediators, histamine and nitrogen peroxide were suggested as biomarkers that can measure electro-hypersensitivity. Also, nitrotyrosine, an indicator of the opening of the blood brain barrier, Protein S100B, and circulating autoantibodies against O-myelin were proposed as biomarkers of electo-hypersensitivity. An increased Hsp27 and Hsp70 expression were observed in animal experiments (Belpomme et al., 2015). The elevation of these factors could cause myelin sheath damage. In addition, early exposure to RF-EMFs increased malondialdehyde and glutathione levels, atrophy and vacuolization of spinal cord, and hypertrophy and irregularization of myelin in the cell body were observed, thus, leading to significant damage to the myelin sheaths and penetration into the axon (İkinci et al., 2016). Therefore, it is suggested that exposure of RF-EMFs may cause biochemical and pathological changes in the spinal cord.
Interestingly, it has been claimed that the symptoms of electro-hypersensitivity due to exposure to RF-EMFs can occur via oligodendrocyte, which plays an important role in myelin formation, much like the neuropathy caused by West Nile virus (Johansson and Redmayne, 2016). Furthermore, it has been proposed as a possible mechanism of neuronal damage and dysfunction due to astrogliosis following exposure to RF-EMFs through observation of glial fibrillary acidic protein (GFAP) increase in the nervous system. In addition, acute exposure of RF-EMFs is suggested as a possible mechanism of neuronal damage and dysfunction. This is due to astrogliosis as a result of exposure to electromagnetic waves observed by GFAP increase in the nervous system (Barthélémy et al., 2016). However, contrary to previous reports, it has been suggested that electromagnetic stimulation may enhance the proliferation and migration of subventricular neural stem cells, thereby reducing the extent of demyelination and promoting remyelination (Sherafat et al., 2012). In neurological diseases, transcranial magnetic stimulation has been shown to improve paralysis and decrease cellular damage due to oxidative stress and to increase antioxidant activity (Medina-Fernandez et al., 2017). These results suggest that there is a possibility of reducing nerve damage in addition to the induction of RF-EMFs damage to the myelin sheath. Therefore, further study is needed to clarify the influence of RF-EMFs on myelin sheaths.
Human beings have developed communication technology along with the development of numerous electronic products in accordance with scientific and technological progresses. Due to these technological developments, the demand for usage of various electronic devices to maintain modern society is continuously increasing, especially the development of wireless communication technologies such as smart phones, which have become a necessity for modern people. In addition, the frequency ranges are continuously widening due to various types of electronic devices are being used. Because mankind uses any electronic devices, electromagnetic fields are generated essentially. Some equipment used in broadcast, communications and transportations also liberated electromagnetic waves to the entire communities. When using any electronic devices, essentially electromagnetic waves are generated. These waves can be absorbed by human or animal bodies, even despite the unintended. Among various electronic devices, smart phones are used close to our body, and the use time has been rapidly increasing recently. Moreover, the use of smartphones has increased not only in adulthood, but also in youth and elderly people including young children. Therefore, there are increasing concerns about the possible biological effects of electromagnetic fields liberated from electronic devices including smart phones. However, there is a lack of information on the possible effects of artificial electromagnetic fields on living organisms liberated from the use of such devices and equipment.
The IARC has classified RF-EMFs as a possibly carcinogenic to humans (Baan et al., 2011) and warms of the danger of EMF exposure. Moreover, it has been hypothesized that a variety of neurological effects may occur as a result of RF-EMF exposure due to the proximity of the cranial nervous system and the location where the cellular phone is predominantly used. These neurological abnormalities include headache (Frey, 1998), changes in sleep habits (Wagner et al., 1998), and changes in EEG (Braune et al., 1998; Mann et al., 1998). In addition, significant statistical results have been reported by various epidemiological studies on neurological cognitive disorders such as headache, tremor, dizziness, memory loss, loss of concentration, and sleep disturbance due to RF-EMF (Kolodynski and Kolodynska, 1996; Santini et al., 2002; Hutter et al., 2006; Abdel-Rassoul et al., 2007). As a possible mechanism for the change of neurological functions by RF-EMFs exposure, we are confident that more mechanisms will be involved than those mentioned, but we have summarized only recent studies on thermal effects, activation of autophagy processes, changes in ion-channel expression, and changes in myelin sheaths in this review (Fig. 3). Most of these studies were performed using cell or animal models and they have provided basic information on the underlying possible biological effects of RF-EMFs exposure to living creatures. So, these results could not apply to humans directly. Precise epidemiological studies are needed to confirm the possible biological effects of RF-EMF exposure to humans. Recently, the governmental regulation on RF-EMFs of individual devices has been introduced to reflect the concern about the biological effect of RF-EMFs. However, the possible biological effects on electromagnetic fields exposure has not yet been well established even in scientific communities. Therefore, it is necessary to apply international standard at the preventive level at least and disclose related information to public in a transparent manner.