Exposure to 900MHz electromagnetic fields activates the mkp-1/ERK pathway and causes blood-brain barrier damage and cognitive impairment in rats
Tang J, Zhang Y, Yang L, Chen Q, Tan L, Zuo S, Feng H, Chen Z, Zhu G. Exposure to 900MHz electromagnetic fields activates the mkp-1/ERK pathway and causes blood-brain barrier damage and cognitive impairment in rats. Brain Res. 2015 Jan 15. pii: S0006-8993(15)00030-X. doi: 10.1016/j.brainres.2015.01.
AbstractWith the rapid increase in the number of mobile phone users, the potential adverse effects of the electromagnetic field radiation emitted by a mobile phone has become a serious concern. This study demonstrated, for the first time, the blood-brain barrier and cognitive changes in rats exposed to 900MHz electromagnetic field (EMF) and aims to elucidate the potential molecular pathway underlying these changes.
A total of 108 male Sprague-Dawley rats were exposed to a 900MHz, 1mW/cm2 EMF or sham (unexposed) for 14 or 28 days (3h per day). The specific energy absorption rate (SAR) varied between 0.016 (whole body) and 2W/kg (locally in the head). In addition, the Morris water maze test was used to examine spatial memory performance determination. Morphological changes were investigated by examining ultrastructural changes in the hippocampus and cortex, and the Evans Blue assay was used to assess blood brain barrier (BBB) damage. Immunostaining was performed to identify heme oxygenase-1 (HO-1)-positive neurons and albumin extravasation detection. Western blot was used to determine HO-1 expression, phosphorylated ERK expression and the upstream mediator, mkp-1 expression.
We found that the frequency of crossing platforms and the percentage of time spent in the target quadrant were lower in rats exposed to EMF for 28 days than in rats exposed to EMF for 14 days and unexposed rats. Moreover, 28 days of EMF exposure induced cellular edema and neuronal cell organelle degeneration in the rat. In addition, damaged BBB permeability, which resulted in albumin and HO-1 extravasation were observed in the hippocampus and cortex. Thus, for the first time, we found that EMF exposure for 28 days induced the expression of mkp-1, resulting in ERK dephosphorylation.
Taken together, these results demonstrated that exposure to 900MHz EMF radiation for 28 days can significantly impair spatial memory and damage BBB permeability in rat by activating the mkp-1/ERK pathway.
To the best of our knowledge, this is the first study to demonstrate that 900 MHz EMF affected spatial memory in rats exposed to EMF for 28 days but not in rats exposed to EMF for 14 days. Furthermore, 900 MHz EMF exposure increased HO-1 immunostaining in the cortex and hippocampus of rats. The percentage of time spent in the target quadrant and the frequency of platform crossing were lower in the rats in the EMF28d group than in the other groups. The rats in the EMF28d group were also less able to recall the precise position of the hidden platform on the day of memory retention despite the 4-day training sessions.
The rats were randomly divided into a non-exposed group, an EMF14d group and an EMF28d group. In the irradiated group, the rats were exposed to radiation at a
power density of 1 mW/cm2, whereas the rats in the non-exposed group were exposed at a power density of 0 W/kg. There were 36 animals in each group and 3 rats were used for electron microscopy, 6 were used for immunohistochemistry, 12 for Evans Blue and 6 for Western blot and 9 rats in each group were used for Morris Water Maze (MWM) test (In Morris Water Maze, the rats need days of training and they are not suitable for any other experiences). All 108 rats were included in the final analysis.
Application of the electromagnetic field and exposure system used in this study have been previously described by Odaci E et al. (Odaci et al., 2008). In the EMF14d group, the rats were exposed to 900 MHz EMF for 3 hours per day for 14 days, and the rats were exposed for 28 days in the EMF28d group. The exposure system consists of a microwave power generator and monopole antenna ... The device could generate 900 MHz continuous electromagnetic waves with 2 W peak output power and 1 mW/cm2 power density in a mobile phone frequency. The specific energy absorption rate (SAR) varied between 0.016 (whole body) and 2 W/kg (locally in the head), which was determined in a phantom.
The present study provides evidence that 900-MHz electromagnetic field exposure resulted in the disruption of BBB permeability, due to an increased occurrence of neuronal albumin in the hippocampus and cortex of rats exposed to EMF for 14 days and 28 days, particularly in rats in the EMF28d group. The ability to learn and remember in rats is dependent on the integrity of relevant structures of the brain, and disrupted BBB permeability by EMF most likely results in ultrastructural changes and increased HO-1 expression in exposed rats. However, the mechanism for the passage of albumin over the BBB is unclear. Extravasation via vesicle-mediated transport across blood vessels, endothelial cells and transendothelial channels may account for this passage (Nittby et al., 2009; Shivers et al., 1987). The extravasation of serum albumin produces secondary neurotoxicity in the brain (Eberhardt et al., 2008; Lai et al., 1992). Albumin is a relatively small molecule, but other substances also have access to the brain and can result in a series of brain injuries. Moreover, the membranes of mitochondria and lysosomes of the residual body type could be affected and may release previously sequestered residual body material, including heavy metals and peroxidized lipid membrane residues.
Although rats in the EMF14d group exhibited changes in ultrastructure and BBB permeability, they showed no significant impairment in spatial memory, as measured using the Morris water maze test. Thus, the time period of exposure may be insufficient to significantly affect spatial memory, and the rats may have the ability to compensate or repair areas affected by EMF exposure to recover normal behavior. A previous study indicated that neural reorganization may allow compensatory strategies to overcome EMF-induced damage and may provide normal task acquisition and subsequent memory retrieval (Martin and Clark, 2007). Another possibility is that the Morris water maze test is not sufficiently sensitive to identify subtle changes in learning and memory.
In conclusion, our results indicate that 900-MHz electromagnetic field exposure attenuated cognitive function, ultrastructural structure and damaged BBB permeability in rat. Thus, for the first time, we found that the mkp-1/ERK signaling pathway may be potentially involved in this process. Because EMF exposure to life is a very complex process, further studies in vivo and in vitro are needed to elucidate the precise dosage and exposure time that are harmful. To better understand this process, further studies are required to investigate the molecular pathways involved in vitro.
Joel M. Moskowitz, Ph.D., Director
Center for Family and Community Health
School of Public Health
University of California, Berkeley
Electromagnetic Radiation Safety
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