López-Martín E, Bregains J, Relova-Quinteiro JL, Cadarso-Suárez C, Jorge-Barreiro FJ, Ares-Pena FJ. The action of pulse-modulated GSM radiation increases regional changes in brain activity and c-FOS expression in cortical and subcortical areas in a rat model of picrotoxin-induced seizure proneness. J Neurosci Res Dec 29, 2008 Ahead of print.

Research suggests that radiofrequency (RF) radiation alters cerebral activity in humans and laboratory animals, and these effects do not appear to be dependent on thermal mechanisms. It has been reported that pulse-modulated RF can modulate the effects of drugs and can affect the function of some neurotransmitters. The expression of c-Fos has been characterized as being elevated in response to various stress or neurotoxic stimuli, such as seizures or physical and nonpathogenic environmental conditions. Thus, c-Fos can be used as a sensitive marker of neuronal activation. In a previous study, the authors found that rats pretreated with a sub-convulsive dose of picrotoxin (PT) and then exposed to GSM radiation showed significant alterations in various indicators of brain activity, including clinical indicators, EEG indicators, and c-Fos levels in the brain.

The aim of the present study was 1) to assess whether the effects on brain activity of pulse-modulated GSM differ from those of non-modulated radiation of the same wavelength and, if so, 2) to study c-Fos expression in seizure-related anatomical circuits.

Rats were assigned to one of the following 6 groups:

Group 1 (PT/no-RAD)

Rats were injected with PT, then immobilized for 2 hours without exposure to radiation

Group 2 (PT/GSM)

Rats were injected with PT, then immobilized for 2 hours with exposure to 900 MHz pulse-modulated GSM radiation

Group 3 (PT/UNMOD)

Rats were injected with PT, then immobilized for 2 hours with exposure to 900 MHz unmodulated radiation

Group 4 (no-PT/no-RAD)

Rats were injected with vehicle only, not PT, and immobilized without exposure to radiation

Group 5 (no-PT/GSM)

Rats were injected with vehicle only, not PT, immobilized and exposed to GSM radiation

Group 6 (no-PT/UNMOD)

Rats were injected with vehicle only, not PT, immobilized and exposed to unnmodulated radiation

All animals were continuously observed and videotaped for 2 hours after intraperitoneal injection of PT. Behavioral modifications, myoclonic jerks, occurrence and latency of convulsive seizures were recorded. Immunohistochemical analysis of brain tissues was conducted to characterize neuronal c-Fos expression.

Results and interpretation
For UNMOD radiation, there was no significant difference in the proportion of c-Fos-immunopositive neurons (c-Fos expression) between PT-treated and PT-untreated rats (PT/UNMOD and no-PT/UNMOD); occasional discharges occurred in EEG recording, and seizure development was infrequent in treated animals. However, GSM radiation induced seizures and increased c-Fos positive neuron counts in animals made seizure-prone by PT treatment. These findings (scarce clinical and EEG signs without GSM and seizures with GSM) suggest that the convulsant drug picrotoxin and GSM radiation had parallel effects via a common mechanism, as was reported for other drugs by other investigators. All SAR values in the four irradiated groups were below thermal values, which, in agreement with findings of other researchers, suggest that GSM radiation is capable of triggering seizures in seizure-prone rats through non-thermal mechanisms. In the absence of pulse modulation (the UNMOD group), the estimated SAR was higher, but still not high enough to trigger seizures by a thermal or other mechanisms. Thus, pulse modulation appears to be essential for triggering seizures and increasing the level of c-Fos. The most marked effects of GSM radiation on c-Fos expression in PT-treated rats were observed in limbic structures, olfactory cortex areas and subcortical areas, the dentate gyyrus, and the central lateral nucleus of the thalamic intralaminar nucleus group. Non-PT treated animals exposed to UNMOD radiation showed the highest levels of neuronal c-Fos expression in cortical areas.

The 900-MHz GSM radiation triggered a marked increase in neuronal excitability in seizure-prone rats, as manifested by behavioral indicators, EEG indicators, and neuronal c-Fos expression, with respect to rats exposed to unmodulated radiation. Signal modulation thus stimulates c-Fos expression in different areas of the limbic system. Participation of these structures in important cognitive processes indicates a clear need to continue studies of the effects of mobile telephone use on brain function.

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