ID Number		89
Study Type		In Vivo
Model		900 MHz (GSM, CW) exposure to rats and analysis of brain pathology and behavior.
Details		Sprague Dawley rats were exposed to 900 MHz (CW, GSM) RF at SARs of 1.5-6 W/kg for 15 minutes using a loop antenna and a Plexiglas restrainer. The authors report decreased binding of NMDA glutamate receptors to 3H-TCP, GABA receptors to 3H-muscimol, and dopamine receptors to 3H-BTCP. GFAP activity was also reported to increase suggesting a glial reaction due to neuronal injury. No effect was observed on locomoter activity in the rats. In a 2004 paper, the authors report 15 minute exposure at 6 W/kg significantly changed [3H] BTCP binding (20% decrease in the cortex, 30% increase in the striatum), significantly decreased NMDAR at the synaptic plasma membrane, and significantly increased glial (GFAP) immunoreactivity in different structures of the rat brain (indicating astrocyte hypertrophy and/or hyperplasia), even 72 hours after exposure. The authors also reported various biochemical changes in neurotransmitter receptor properties, although no evidence of such changes were observed in open-field behavior tests. The authors initially concluded that the results suggested neuronal damage provoked by local over-activation of the glutamatergic system and/or imbalance between excitatory and inhibitory systems. However, the lack of behavioral effects questioned whether the observations were directly extrapolatable to an adverse effect in humans. In a subsequent follow-up study to determine if the GFAP effect was transient or long-term, as well as to see if any dose response gradient within the brain could be established, the authors exposed rats as above (6 W/kg for 15 minutes) using the loop antenna and examined histological sections with immuno-staining in rats from 1 to 10 days post-exposure. Increased GFAP staining nearest the loop antenna (at the region of highest local SAR) lasted 3 days following exposure to 900 Mhz (GSM), but disappeared by day 6 and 10. The authors interpreted this result as a transient RF-induced inflammation. The authors further reported significant temperature increases in the brain in the zone near the loop antenna, and suggested the observed effects were likely due to heating. In a 2007 paper, the authors used a single 15 minute exposure as above at 6 W/kg and reported a statistically significant increase in GFAP in the frontal cortex and caudate putamen even after 2 days post exposure that returned to baseline after 3 days post exposure, suggesting transient increased glial reactivity and could be associated with direct activation of the cortex. The effect also decreased in the cortex with distance from the antenna, suggesting a dose response. In a subsequent study using the same 900 MHz (GSM)exposure system at either 1.5 W/kg (for 45 min/day, 5 days/wk, 24 weeks) or 6 W/kg (for 15 min/day, 5 days/wk, 24 weeks). The authors report that the number of reactive astrocytes in the prefrontal cortex (recieving the most RF energy from the exposure)as well as the denate gyrus, caudate putamen, and LGP increased in the 6 W/kg group, but not in the 1.5 W/kg group suggesting the effect was not due to total energy absorption but peak SAR (and perhaps due to heating). Another study using the same exposure system and conditions reported decreased cytochrome C oxidase activity (a marker for neuron metabolic activity) in several regions of the cortex, septum, and hippocampus of animals exposed 15 minutes/day for 7 days at 6 W/kg, but not in animals exposed 45 minutes/day for 7 days at 1.5 W/kg. Spatial memory function, however, was not affected by the above exposures. AUTHORS' ABSTRACT: Bouji, de Seze et al. 2012 IEEE #6251): The widespread use of mobile phones raises the question of the effects of electromagnetic fields (EMF, 900 MHz) on the brain. Previous studies reported increased levels of the glial fibrillary acidic protein (GFAP) in the rat's brain after a single exposure to 900 MHz global system for mobile (GSM) signal, suggesting a potential inflammatory process. While this result was obtained in adult rats, no data is currently available in older animals. Since the transition from middle-age to senescence is highly dependent on environment and lifestyle, we studied the reactivity of middle-aged brains to EMF exposure. We assessed the effects of a single 15 min GSM exposure (900 MHz; specific absorption rate (SAR)=6 W/kg) on GFAP expression in young adults (6 week-old) and middle-aged rats (12 month-old). Brain interleukin (IL)-1² and IL-6, plasmatic levels of corticosterone (CORT), and emotional memory were also assessed. Our data indicated that, in contrast to previously published work, acute GSM exposure did not induce astrocyte activation. Our results showed an IL-1² increase in the olfactory bulb and enhanced contextual emotional memory in GSM-exposed middle-aged rats, and increased plasmatic levels of CORT in GSM-exposed young adults. Altogether, our data showed an age dependency of reactivity to GSM exposure in neuro-immunity, stress and behavioral parameters. Reproducing these effects and studying their mechanisms may allow a better understanding of mobile phone EMF effects on neurobiological parameters. AUTHORS' ABSTRACT: Ammari, De Seze et al. 2010 (IEEE #6259): PURPOSE: The rapid development and expansion of mobile communications contributes to the general debate on the effects of electromagnetic fields emitted by mobile phones on the nervous system. This study aims at measuring the glial fibrillary acidic protein (GFAP) expression in 48 rat brains to evaluate reactive astrocytosis, three and 10 days after long-term head-only sub-chronic exposure to a 900 MHz electromagnetic field (EMF) signal, in male rats. METHODS: Sprague-Dawley rats were exposed for 45 min/day at a brain-averaged specific absorption rate (SAR) = 1.5 W/kg or 15 min/day at a SAR = 6 W/kg for five days per week during an eight-week period. GFAP expression was measured by the immunocytochemistry method in the following rat brain areas: Prefrontal cortex, cerebellar cortex, dentate gyrus of the hippocampus, lateral globus pallidus of the striatum, and the caudate putamen. RESULTS: Compared to the sham-treated rats, those exposed to the sub-chronic GSM (Global System for mobile communications) signal at 1.5 or 6 W/kg showed an increase in GFAP levels in the different brain areas, three and ten days after treatment. CONCLUSION: Our results show that sub-chronic exposures to a 900 MHz EMF signal for two months could adversely affect rat brain (sign of a potential gliosis). AUTHORS' ABSTRACT: Barthelemy et al. 2016 (IEEE #6522): The widespread mobile phone use raises concerns on the possible cerebral effects of radiofrequency electromagnetic fields (RF EMF). Reactive astrogliosis was reported in neuroanatomical structures of adaptive behaviors after a single RF EMF exposure at high specific absorption rate (SAR, 6 W/kg). Here, we aimed to assess if neuronal injury and functional impairments were related to high SAR-induced astrogliosis. In addition, the level of beta amyloid 1-40 (A² 1-40) peptide was explored as a possible toxicity marker. Sprague Dawley male rats were exposed for 15 min at 0, 1.5, or 6 W/kg or for 45 min at 6 W/kg. Memory, emotionality, and locomotion were tested in the fear conditioning, the elevated plus maze, and the open field. Glial fibrillary acidic protein (GFAP, total and cytosolic fractions), myelin basic protein (MBP), and A²1-40 were quantified in six brain areas using enzyme-linked immunosorbent assay. According to our data, total GFAP was increased in the striatum (+114 %) at 1.5 W/kg. Long-term memory was reduced, and cytosolic GFAP was increased in the hippocampus (+119 %) and in the olfactory bulb (+46 %) at 6 W/kg (15 min). No MBP or A²1-40 expression modification was shown. Our data corroborates previous studies indicating RF EMF-induced astrogliosis. This study suggests that RF EMF-induced astrogliosis had functional consequences on memory but did not demonstrate that it was secondary to neuronal damage.
Findings		Effects
Status		Completed With Publication
Principal Investigator		University of Montpillier, France - biomed@zeus.sc.univ-montpl.fr
Funding Agency		France Telecom/CNET, CoMoBio, France, RAMP, EU 5th Framework, Europe, FSR, France
Country		FRANCE
References		Ammari, M et al. Brain Inj, (2008) 22:1021-1029 Ammari, M et al. Toxicology, (2008) 250:70-74 Ammari, M et al. Biomed Pharmacother, (2008) 62:273-281 Brillaud, E et al. Toxicol, (2007) 238:23-33 Mausset-Bonnefont , AL et al. Neurobiology of Disease, (2004) 17:445-454 Mausset, A et al. Brain Res., (2001) 912:33-46 Bouji, M et al. Exp Gerontol., (2012) 47:444-451 Ammari, M et al. Int J Radiat Biol., (2010) 86:367-375 Barthelemy, A et al. Environ Sci Pollut Res Int., (2016) 23:25343-25355 Bouji, M et al. J Alzheimers Dis. , (2020) 73:467-476 Ouadah, NS et al. International Journal of Environmental Research and Public Health., (2020) 17:7563- Ghosn, R et al. Radiation research., (2012) 178:543-550 Petitdant, N et al. Environmental science and pollution research international., (2018) 25:10894-10903
Comments		Using this exposure system, average SARs within the brain are reported as 1.5, 4, and 6 W/kg, but peak SARs in the peripheral brain regions may have been much higher, especially given dosimetry studies using a similar exposure system performed by Battelle (Anderson et al). Initial temperature assessment was limited to readings from a Vitek (optical) temperature probe placed at the center of the brain area in an acrylic plastic model phantom, with temperature still increasing 0.58 oC following exposure (Veyret personal communication). In addition, the Brillaud 2007 study placed a Luxtron (optical) probe on the head (skin) of live exposed and sham exposed animals and reported temperature increases of ~5oC from initial ambient (presumably due to the restraint). Further, temperature went up much faster in the first 5 minutes in the RF exposed animals vs sham. While the temperature profile within the peripheral regions of the brain in exposed animals is not know, it is possible some temperature elevations were experienced. Finally, the authors do not report the normal range of variability for many of the immunohistologic parameters measured, no dose-response, and no control with known inhibitors or stimulants.