Short-term 2.1 GHz radiofrequency radiation treatment induces significant changes on the auditory evoked potentials in adult rats.

PURPOSE: There is a growing interest in the usage of radiofrequency radiation (RF) as a noninvasive brain stimulation method. Previously reported data demonstrated that RF exposure caused a change in brain oscillations. Therefore, we aimed to investigate effects of RF on brain oscillation by measuring the auditory response of different brain regions in rats. MATERIALS AND METHODS: Rats were randomly divided into three groups (n = 12 per each group): Cage control (C), sham rats (Sh), and rats exposed to 2.1 GHz RF for 2 h/day for 7 days. At the end of the exposure, auditory evoked potentials (AEPs) were recorded at different locations in rats. Latencies and amplitudes of AEPs, evoked power, inter-trial phase synchronization, and auditory evoked gamma responses were obtained in response to an auditory stimulus. Furthermore, TBARS levels and 4-HNE, GFAP, iNOS, and nNOS expressions were evaluated in all groups. RESULTS: Peak-to-peak amplitudes of AEPs were significantly higher in the RF group compared with the Sh group. There is no significant difference in peak latencies of AEPs between groups. Beside, evoked power, inter-trial phase synchronization, and auditory evoked gamma responses were significantly higher in the RF group compared with the Sh group. In addition, the RF group had significantly lower TBARS and 4-HNE levels than the Sh group. There were no significant differences between groups for GFAP, nNOS, and iNOS levels, and between the C and RF groups for all parameters. CONCLUSIONS: Our present findings suggest that short-term RF treatment under chosen experimental conditions have statistically significant effect on neuronal networks of rats by probably reducing oxidative damage. However, this effect must be further studied for possible noninvasive brain stimulation.

Protective role of rosmarinic acid on amyloid beta 42-induced echoic memory decline: Implication of oxidative stress and cholinergic impairment.

In the present study, we examined whether rosmarinic acid (RA) reverses amyloid ß (Aß) induced reductions in antioxidant defense, lipid peroxidation, cholinergic damage as well as the central auditory deficits. For this purpose, Wistar rats were randomly divided into four groups; Sham(S), Sham + RA (SR), Aß42 peptide (Aß) and Aß42 peptide + RA (AßR) groups. Rat model of Alzheimer was established by bilateral injection of Aß42 peptide (2,2 nmol/10 µl) into the lateral ventricles. RA (50 mg/kg, daily) was administered orally by gavage for 14 days after intracerebroventricular injection. At the end of the experimental period, we recorded the auditory event related potentials (AERPs) and mismatch negativity (MMN) response to assess auditory functions followed by histological and biochemical analysis. Aß42 injection led to a significant increase in the levels of thiobarbituric acid reactive substances (TBARS) and 4-Hydroxy-2-nonenal (4-HNE) but decreased the activity of antioxidant enzymes (SOD, CAT, GSH-Px) and glutathione levels. Moreover, Aß42 injection resulted in a reduction in the acetylcholine content and acetylcholine esterase activity. RA treatment prevented the observed alterations in the AßR group. Furthermore, RA attenuated the increased Aß staining and astrocyte activation. We also found that Aß42 injection decreased the MMN response and theta power/coherence of AERPs, suggesting an impairing effect on auditory discrimination and echoic memory processes. RA treatment reversed the Aß42 related alterations in AERP parameters. In conclusion, our study demonstrates that RA prevented Aß-induced antioxidant-oxidant imbalance and cholinergic damage, which may contribute to the improvement of neural network dynamics of auditory processes in this rat model.

Alterations in spontaneous delta and gamma activity might provide clues to detect changes induced by amyloid-ß administration.

Alzheimer's disease (AD) is the most prevalent form of dementia and has an increasing incidence. The neuropathogenesis of AD is suggested to be a result of the accumulation of amyloid-ß (Aß) peptides in the brain. To date, Aß-induced cognitive and neurophysiologic impairments have not been illuminated sufficiently. Therefore, we aimed to examine how spontaneous brain activities of rats changed by injection of increasing Aß doses into the brain hemispheres, and whether these changes could be used as a new biomarker for the early diagnosis of the AD. Rats were randomized into following groups: sham (Sham) and seven Aß-treated (i.c.v.) groups in increasing concentrations (from Aß-1 to Aß-7). After recovery, EEG recordings were obtained from implanted electrodes from eight electrode locations, and then, spectral and statistical analyses were performed. A significant decrement in gamma activity was observed in all Aß groups compared with the sham group. In delta activity, we observed significant changes from Aß-4 to Aß-7 group compared with sham group. Delta coherence values were decreased from Aß-4 to Aß-7 and Aß-5 to Aß-7 groups for frontal and temporal electrode pairs, respectively. A gradual increment was observed in Aß1-42 level till Aß-4 group. Positive correlation for global delta power and negative correlation for global gamma power between Aß1-42 peptide levels were detected. Consequently, it is conceivable to suggest gamma oscillation might be used to detect early stages of AD. Moreover, changes in delta activity provide information about the onset of major pathologic changes in the progress of AD.

Effects of acute and chronic exposure to both 900 MHz and 2100 MHz electromagnetic radiation on glutamate receptor signaling pathway.

PURPOSE: To demonstrate the molecular effects of acute and chronic exposure to both 900 and 2100 MHz radiofrequency electromagnetic radiation (RF-EMR) on the hippocampal level/activity of some of the enzymes - including PKA, CaMKIIα, CREB, and p44/42 MAPK - from N-methyl-D-aspartate receptor (NMDAR)-related signaling pathways. MATERIALS AND METHODS: Rats were divided into the following groups: sham rats, and rats exposed to 900 and 2100 MHz RF-EMR for 2 h/day for acute (1 week) or chronic (10 weeks), respectively. Western blotting and activity measurement assays were used to assess the level/activity of the selected enzymes. RESULTS: The obtained results revealed that the hippocampal level/activity of selected enzymes was significantly higher in the chronic groups as compared to the acute groups at both 900 and 2100 MHz RF-EMR exposure. In addition, hippocampal level/activity of selected enzymes was significantly higher at 2100 MHz RF-EMR than 900 MHz RF-EMR in both acute and chronic groups. CONCLUSIONS: The present study provides experimental evidence that both exposure duration (1 week versus 10 weeks) and different carrier frequencies (900 vs. 2100 MHz) had different effects on the protein expression of hippocampus in Wistar rats, which might encourage further research on protection against RF-EMR exposure.

Changes of auditory event-related potentials in ovariectomized rats injected with d-galactose: Protective role of rosmarinic acid.

Rosmarinic acid (RA), which has multiple bioactive properties, might be a useful agent for protecting central nervous system against age related alterations. In this context, the purpose of the present study was to investigate possible protective effects of RA on mismatch negativity (MMN) component of auditory event-related potentials (AERPs) as an indicator of auditory discrimination and echoic memory in the ovariectomized (OVX) rats injected with d-galactose combined with neurochemical and histological analyses. Ninety female Wistar rats were randomly divided into six groups: sham control (S); RA-treated (R); OVX (O); OVX+RA-treated (OR); OVX+d-galactose-treated (OD); OVX+d-galactose+RA-treated (ODR). Eight weeks later, MMN responses were recorded using the oddball condition. An amplitude reduction of some components of AERPs was observed due to ovariectomy with or without d-galactose administiration and these reduction patterns were diverse for different electrode locations. MMN amplitudes were significantly lower over temporal and right frontal locations in the O and OD groups versus the S and R groups, which was accompanied by increased thiobarbituric acid reactive substances (TBARS) and hydroxy-2-nonenal (4-HNE) levels. RA treatment significantly increased AERP/MMN amplitudes and lowered the TBARS/4-HNE levels in the OR and ODR groups versus the O and OD groups, respectively. Our findings support the potential benefit of RA in the prevention of auditory distortion related to the estrogen deficiency and d-galactose administration at least partly by antioxidant actions.

Glucocorticoids mediate stress-induced impairment of retrieval of stimulus-response memory.

Acute stress and elevated glucocorticoid hormone levels are well known to impair the retrieval of hippocampus-dependent 'declarative' memory. Recent findings suggest that stress might also impair the retrieval of non-hippocampal memories. In particular, stress shortly before retention testing was shown to impair the retrieval of striatal stimulus-response associations in humans. However, the mechanism underlying this stress-induced retrieval impairment of non-hippocampal stimulus-response memory remains elusive. In the present study, we investigated whether an acute elevation in glucocorticoid levels mediates the impairing effects of stress on retrieval of stimulus-response memory. Male Sprague-Dawley rats were trained on a stimulus-response task in an eight-arm radial maze until they learned to associate a stimulus, i.e., cue, with a food reward in one of the arms. Twenty-four hours after successful acquisition, they received a systemic injection of vehicle, corticosterone (1mg/kg), the corticosterone-synthesis inhibitor metyrapone (35mg/kg) or were left untreated 1h before retention testing. We found that the corticosterone injection impaired the retrieval of stimulus-response memory. We further found that the systemic injection procedure per se was stressful as the vehicle administration also increased plasma corticosterone levels and impaired the retrieval of stimulus-response memory. However, memory retrieval was not impaired when rats were tested 2min after the systemic vehicle injection, before any stress-induced elevation in corticosterone levels had occurred. Moreover, metyrapone treatment blocked the effect of injection stress on both plasma corticosterone levels and memory retrieval impairment, indicating that the endogenous corticosterone response mediates the stress-induced memory retrieval impairment. None of the treatments affected rats' locomotor activity or motivation to search for the food reward within the maze. These findings show that stress may affect memory processes beyond the hippocampus and that these stress effects are due to the action of glucocorticoids.

2100-MHz electromagnetic fields have different effects on visual evoked potentials and oxidant/antioxidant status depending on exposure duration.

The purpose of the present study was to investigate the duration effects of 2100-MHz electromagnetic field (EMF) on visual evoked potentials (VEPs) and to assess lipid peroxidation (LPO), nitric oxide (NO) production and antioxidant status of EMF exposed rats. Rats were randomized to following groups: Sham rats (S1 and S10) and rats exposed to 2100-MHz EMF (E1 and E10) for 2h/day for 1 or 10 weeks, respectively. At the end of experimental periods, VEPs were recorded under anesthesia. Brain thiobarbituric acid reactive substances (TBARS) and 4-hydroxy-2-nonenal (4-HNE) levels were significantly decreased in the E1 whereas increased in the E10 compared with their control groups. While brain catalase (CAT), glutathione peroxidase (GSH-Px) activities and NO and glutathione (GSH) levels were significantly increased in the E1, reduction of superoxide dismutase (SOD) activity was detected in the same group compared with the S1. Conversely, decreased CAT, GSH-Px activities and NO levels were observed in the E10 compared with the S10. Latencies of all VEP components were shortened in the E1 compared with the S1, whereas latencies of all VEP components, except P1, were prolonged in the E10 compared with the S10. There was a positive correlation between all VEP latencies and brain TBARS and 4-HNE values. Consequently, it could be concluded that different effects of EMFs on VEPs depend on exposure duration. In addition, our results indicated that short-term EMF could provide protective effects, while long-term EMF could have an adverse effect on VEPs and oxidant/antioxidant status.

Effects of rosmarinic acid on cognitive and biochemical alterations in ovariectomized rats treated with D-galactose.

INTRODUCTION: Animal models designed to mimic certain features of Alzheimer's disease (AD) can help us to increase our understanding of the underlying mechanisms of disease. Previous studies have revealed that long-term D-galactose injection combined with ovariectomy results in pathophysiologic alterations associated with AD. Thus, the aim of the present study was to investigate the effects of rosmarinic acid (RA) administration on pathological changes associated with ovariectomy and D-galactose injection, which serve as a two-insult model for AD. MATERIAL AND METHODS: One hundred female Wistar rats were divided into five equal groups: control (C), Sham (Sh), rosmarinic acid treated (R), ovariectomized rats treated with D-galactose (OD), ovariectomized rats treated with D-galactose and rosmarinic acid (ODR) groups. D-galactose (80 mg/kg/day) was administered by i.p. injection and RA (50 mg/kg/day) was given via gavage for 60 days. Open field and Y-maze tests were used to assess locomotor activity and short-term spatial memory, respectively. Biochemical and histopathological analyses of the brain tissue were performed. RESULTS: Open field testing showed that the locomotor activity and exploratory behavior of rats were prominently impaired in the OD group as compared to the other studied groups. Similarly, Y-maze test results revealed a decrease of short-term spatial memory in the OD rats. A concomitant treatment with RA significantly restored altered locomotor activity and cognitive functions in the ODR group. Lipid peroxidation levels, cyclooxygenase-2 expression and prostaglandin E2 levels in the brain tissue were higher in the OD group and RA treatment inhibited these changes. AD-like histopathological alterations and amyloid b peptide (Ab) depositions were observed in the OD group. Normal cell structure and lower Ab depositions were observed in the ODR group compared with the OD group. CONCLUSIONS: RA could have the potential to prevent some psychological and biochemical alterations of brain tissue found in a rat model of AD probably by attenuating lipid peroxidation and inflammatory response.