Expression levels of tam receptors and ligands in the testes of rats exposed to short and middle-term 2100 MHz radiofrequency radiation.

With advances in technology, the emission of radiofrequency radiation (RFR) into the environment, particularly from mobile devices, has become a growing concern. Tyro 3, Axl, and Mer (TAM) receptors and their ligands are essential for spermatogenesis and testosterone production. RFR has been shown to induce testicular cell apoptosis by causing inflammation and disrupting homeostasis. This study aimed to investigate the role of TAM receptors and ligands in the maintenance of homeostasis and elimination of apoptotic cells in the testes (weeks), short-term sham exposure (sham/1 week), and middle-term sham exposure (sham/10 weeks). Testicular morphology was assessed using hematoxylin-eosin staining, while immunohistochemical staining was performed to assess expression levels of TAM receptors and ligands in the testes of all groups. The results showed that testicular morphology was normal in the control, sham/1 week, and sham/10 weeks groups. However, abnormal processes of spermatogenesis and seminiferous tubule morphology were observed in RFR exposure groups. Cleaved Caspase 3 immunoreactivity showed statistically significant difference in 1 and 10 weeks exposure groups compared to control group. Moreover, there was no significant difference in the immunoreactivity of Tyro 3, Axl, Mer, Gas 6, and Pros 1 between groups. Moreover, Tyro 3 expression in Sertoli cells was statistically significantly increased in RFR exposure groups compared to the control. Taken together, the results suggest that RFR exposure negatively affects TAM signalling, preventing the clearance of apoptotic cells, and this process may lead to infection and inflammation. As a result, rat testicular morphology and function may be impaired.

Investigation of Cyclo-Z Therapeutic Effect on Insulin Pathway in Alzheimer's Rat Model: Biochemical and Electrophysiological Parameters.

Cyclo (his-pro-CHP) plus zinc (Zn+2) (Cyclo-Z) is the only known chemical that increases the production of insulin-degrading enzyme (IDE) and decreases the number of inactive insulin fragments in cells. The aim of the present study was to systematically characterize the effects of Cyclo-Z on the insulin pathway, memory functions, and brain oscillations in the Alzheimer's disease (AD) rat model. The rat model of AD was established by bilateral injection of Aß42 oligomer (2,5nmol/10µl) into the lateral ventricles. Cyclo-Z (10mg Zn+2/kg and 0.2mg CHP/kg) gavage treatment started seven days after Aß injection and lasted for 21 days. At the end of the experimental period, memory tests and electrophysiological recordings were performed, which were followed by the biochemical analysis. Aß42 oligomers led to a significant increase in fasting blood glucose, serum insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and phospho-tau-Ser356 levels. Moreover, Aß42 oligomers caused a significant decrement in body weight, hippocampal insulin, brain insulin receptor substrate (IRS-Ser612), and glycogen synthase kinase-3 beta (GSK-3ß) levels. Also, Aß42 oligomers resulted in a significant reduction in memory. The Cyclo-Z treatment prevented the observed alterations in the ADZ group except for phospho-tau levels and attenuated the increased Aß42 oligomer levels in the ADZ group. We also found that the Aß42 oligomer decreased the left temporal spindle and delta power during ketamine anesthesia. Cyclo-Z treatment reversed the Aß42 oligomer-related alterations in the left temporal spindle power. Cyclo-Z prevents Aß oligomer-induced changes in the insulin pathway and amyloid toxicity, and may contribute to the improvement of memory deficits and neural network dynamics in this rat model.

Anxiolytic-like effects of extremely low frequency electric field in stressed rats: involvement of 5-HT2C receptors.

BACKGROUND: Possible modulatory effects of noninvasive brain stimulation have gained interest recently. In our study, the effect of low frequency electric fields (LF-EF) on stress-induced electrophysiological, behavioral changes and the possible involvement of serotonergic 5-HT2C receptors were investigated. MATERIALS AND METHODS: A total of eight groups including the control groups were formed by applying LF-EF with or without a 5-HT2C receptor agonist to naïve or acute stress exposed rats to demonstrate the effects of LF-EF. LF-EF administration at 10 kV/m was started 30 min before acute stress application and lasted for 1 h in total. Anxiety levels and social interaction were evaluated using the elevated plus maze test and social interaction test, respectively. Auditory evoked potentials (AEP) were recorded by using ascending loudness paradigms. Loudness dependence AEP (LDAEP) was calculated by using amplitude values to analyze serotonergic transmission. Serotonin and glucocorticoid levels were measured in the frontal cortex and hippocampus. RESULTS: It was observed that the applied LF-EF reduced the anxiety behavior, and attenuated the LDAEP responses in stress and/or 5-HT2C receptor agonist applied groups. In parallel, an increase in serotonin levels and a decrease in glucocorticoid levels were observed. However, LF-EF exposure was ineffective in impaired social interaction. CONCLUSIONS: Our findings show that 10 kV/m LF-EF administration may modulate the neural network and physiological responses associated with mild acute stress. 5-HT2C receptor dependent functions are thought to play a role in the anxiolytic effect of LF-EF.

Cognitive dysfunctions and spontaneous EEG alterations induced by hippocampal amyloid pathology in rats.

PURPOSE: We aimed to determine the effects of different doses of amyloid-beta (Aß) peptide on learning and memory, and whether the changes in brain oscillations induced by dose-dependent accumulation of Aß could be used as biomarkers to detect early stages of Alzheimer's disease (AD). MATERIAL AND METHODS: Male albino Wistar rats aged 3 months were randomly divided into four groups (n â€‹= â€‹12/group) obtained by i. h. Injection (to the dorsal hippocampus) of saline or different doses of 0.01 â€‹µg/µl, 0.1 â€‹µg/µl, and 1 â€‹µg/µl of Aß. After two weeks of recovery period, open field and novel object recognition tests were performed and spontaneous EEG recordings were obtained. Later, hippocampus tissues were collected for Western blot and ELISA analysis. RESULTS: A significant decrement in recognition memory was observed in 0.1 â€‹µg/µl, and 1 â€‹µg/µl injected groups. In addition, Aß accumulation induced significant decrement of the expression of NeuN, SNAP-25, SYP, and PSD-95 proteins, and led to the increment of GFAP expression in hippocampus. Moreover, we detected remarkable alterations in spontaneous brain activity. The hippocampal Aß levels were negatively correlated with hippocampal gamma power and positively correlated with hippocampal theta power. Also, we observed significant changes in coherence values, indicating the functional connectivity between different brain regions, after the accumulation of Aß. Especially, there was a significant correlation between changes in frontohippocampal theta coherence and in frontotemporal theta coherence. CONCLUSIONS: Our findings indicate that Aß peptide induces AD-like molecular changes at certain doses, and these changes could be detected by evaluating brain oscillations.

The effects of acute and chronic exposure to 900 MHz radiofrequency radiation on auditory brainstem response in adult rats.

The aim of this study was to determine the effects of short and long-term RFR exposure on ABR by evaluating lipid peroxidation and antioxidant status in adult rats. Sixty male albino Wistar rats were randomly divided into four groups. S1:1 week sham, S10:10 weeks sham, E1:1 week RFR, E10:10 weeks RFR. Experimental group rats were exposed to RFR 2 h/day, 5 days/week during the test period. Sham rats were kept in the same conditions without RFR. After the experiment, ABRs were recorded from the mastoids of rats using tone burst acoustic stimuli. Biochemical investigations in rat brain and ultrastructural analysis in temporal cortex were performed. ABR wave I latency prolonged in E1-group and shortened in E10-group compared to their shams. TBARS level increased in E1-group, decreased in E10-group, on the contrary, SOD and CAT activities and GSH level decreased in E1-group, increased in E10-group compared to their sham groups. Edema was present in the neuron and astrocyte cytoplasms and astrocyte end-feet in both E1 and E10 groups. Our results suggest that 900 MHz RFR may have negative effects on the auditory system in acute exposure and no adverse effects in chronic exposure without weekends.

Auditory evoked potentials might have the potential to serve as early indicators related to amyloid beta peptide toxicity.

PURPOSE: Accumulation of amyloid beta (Aß) is thought to be the major cause of the development and progression of Alzheimer's disease (AD). The aim of this study is to elucidate the effects of Aß1-42 at increasing concentrations on auditory evoked potentials (AEPs) and to determine possible changes relevant to the accumulation of Aß1-42. MATERIALS AND METHODS: In this study, rats were randomized to following groups (n = 10 per group): sham (0.9% NaCl), Aß-1 (1 µg/µl), Aß-2 (2 µg/µl), Aß-3 (3 µg/µl), Aß-4 (4 µg/µl), Aß-5 (6 µg/µl), Aß-6 (8 µg/µl) and Aß-7 (10 µg/µl) groups obtained by injection of 5 µl per ventricle. Then, AEPs were recorded in freely-moving rats. Latencies and amplitudes of AEPs, evoked power, inter-trial phase synchronization, and auditory evoked gamma responses were obtained in response to auditory stimulus. Furthermore, Aß1-42 levels were determined in the temporal cortex. RESULTS: Aß1-42 levels were significantly higher in the temporal cortex in Aß groups compared to the sham. In frontal and parietal regions, P1N1 amplitudes were significantly decreased in Aß-3, 4, 5 and 6 groups, and N1P2 amplitudes were significantly decreased in all Aß groups, whereas in temporal regions, P1N1 and N1P2 amplitudes were decreased in Aß-2,3,4,5,6 and 7 compared to the sham. In the evoked gamma power and phase synchronization of gamma responses, we detected significant decrease after Aß-4 group, whereas a significant decrease in the filtered gamma responses was observed in Aß groups compared to the sham. CONCLUSIONS: AEPs might be used as a biomarker to determine the Aß1-42 related neuronal degeneration in the auditory networks.

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.

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.

The effect of ingested sulfite on active avoidance in normal and sulfite oxidase-deficient aged rats.

The aim of this study was to investigate the possible toxic effects of sulfite on neurons by measuring active avoidance learning in normal and sulfite oxidase (SOX)-deficient aged rats. Twenty-four months of age Wistar rats were divided into four groups: control (C), sulfite-treated group (S), SOX-deficient group (D) and SOX-deficient + sulfite-treated group (DS). SOX deficiency was established by feeding rats with a low molybdenum (Mo) diet and adding 200 ppm tungsten (W) to their drinking water. Sulfite in the form of sodium metabisulfite (25 mg/kg) was given by gavage for six weeks. Active avoidance responses were determined by using an automated shuttle box. Hepatic SOX activity was measured to confirm SOX deficiency. The hippocampus was used for determining the activity of cyclooxygenase (COX) and caspase-3 enzymes and the level of prostaglandin E2 (PGE2) and nitrate/nitrite. SOX-deficient rats had an approximately 10-fold decrease in hepatic SOX activity compared with normal rats. Sulfite did not induce impairment of active avoidance learning in SOX-deficient rats and in normal rats compared with their control groups. Sulfite had no effect on the activity of COX and caspase-3 in the hippocampus. Treatment with sulfite did not significantly increase the level of PGE2 and nitrate/nitrite in the hippocampus.

Effects of pre- and postnatal exposure to extremely low-frequency electric fields on mismatch negativity component of the auditory event-related potentials: Relation to oxidative stress.

In our previous study, the developmental effects of extremely low-frequency electric fields (ELF-EF) on visual and somatosensory evoked potentials in adult rats were studied. There is no study so far examining the effects of 50 Hz electric field (EF) on mismatch negativity (MMN) recordings after exposure of rats during development. Therefore, our present study aimed to investigate MMN and oxidative brain damage in rats exposed to EF (12 kV/m, 1 h/day). Rats were divided into four groups, namely control (C), prenatal (Pr), postnatal (Po), and prenatal+postnatal (PP). Pregnant rats of Pr and PP groups were exposed to EF during pregnancy. Following birth, rats of PP and Po groups were exposed to EF for three months. After exposure to EF, MMN was recorded by electrodes positioned stereotaxically to the surface of the dura, and then brain tissues were removed for histological and biochemical analyses. The MMN amplitude was higher to deviant tones than to standard tones. It was decreased in all experimental groups compared with the C group. 4-Hydroxy-2-nonenal (4-HNE) levels were significantly increased in the Po group with respect to the C group, whereas they were significantly decreased in the PP group compared with Pr and Po groups. Protein carbonyl levels were significantly decreased in the PP group compared with C, Pr, and Po groups. EF decreased MMN amplitudes were possibly induced by lipid peroxidation.

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.

The developmental effects of extremely low frequency electric fields on visual and somatosensory evoked potentials in adult rats.

The purpose of our study was to investigate the developmental effects of extremely low frequency electric fields (ELF-EFs) on visual evoked potentials (VEPs) and somatosensory-evoked potentials (SEPs) and to examine the relationship between lipid peroxidation and changes of these potentials. In this context, thiobarbituric acid reactive substances (TBARS) levels were determined as an indicator of lipid peroxidation. Wistar albino female rats were divided into four groups; Control (C), gestational (prenatal) exposure (Pr), gestational+ postnatal exposure (PP) and postnatal exposure (Po) groups. Pregnant rats of Pr and PP groups were exposed to 50 Hz electric field (EF) (12 kV/m; 1 h/day), while those of C and Po groups were placed in an inactive system during pregnancy. Following parturition, rats of PP and Po groups were exposed to ELF-EFs whereas rats of C and Pr groups were kept under the same experimental conditions without being exposed to any EF during 68 days. On postnatal day 90, rats were prepared for VEP and SEP recordings. The latencies of VEP components in all experimental groups were significantly prolonged versus C group. For SEPs, all components of PP group, P2, N2 components of Pr group and P1, P2, N2 components of Po group were delayed versus C group. As brain TBARS levels were significantly increased in Pr and Po groups, retina TBARS levels were significantly elevated in all experimental groups versus C group. In conclusion, alterations seen in evoked potentials, at least partly, could be explained by lipid peroxidation in the retina and brain.

The effect of ingested sulfite on visual evoked potentials, lipid peroxidation, and antioxidant status of brain in normal and sulfite oxidase-deficient aged rats.

Sulfite, commonly used as a preservative in foods, beverages, and pharmaceuticals, is a very reactive and potentially toxic molecule which is detoxified by sulfite oxidase (SOX). Changes induced by aging may be exacerbated by exogenous chemicals like sulfite. The aim of this study was to investigate the effects of ingested sulfite on visual evoked potentials (VEPs) and brain antioxidant statuses by measuring superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities. Brain lipid oxidation status was also determined via thiobarbituric acid reactive substances (TBARS) in normal- and SOX-deficient aged rats. Rats do not mimic the sulfite responses seen in humans because of their relatively high SOX activity level. Therefore this study used SOX-deficient rats since they are more appropriate models for studying sulfite toxicity. Forty male Wistar rats aged 24 months were randomly assigned to four groups: control (C), sulfite (S), SOX-deficient (D) and SOX-deficient + sulfite (DS). SOX deficiency was established by feeding rats with low molybdenum (Mo) diet and adding 200 ppm tungsten (W) to their drinking water. Sulfite in the form of sodium metabisulfite (25 mg kg(-1) day(-1)) was given by gavage. Treatment continued for 6 weeks. At the end of the experimental period, flash VEPs were recorded. Hepatic SOX activity was measured to confirm SOX deficiency. SOX-deficient rats had an approximately 10-fold decrease in hepatic SOX activity compared with the normal rats. The activity of SOX in deficient rats was thus in the range of humans. There was no significant difference between control and treated groups in either latence or amplitude of VEP components. Brain SOD, CAT, and GPx activities and brain TBARS levels were similar in all experimental groups compared with the control group. Our results indicate that exogenous administration of sulfite does not affect VEP components and the antioxidant/oxidant status of aged rat brains.

The Effect of Magnesium on Visual Evoked Potentials in L-NAME-Induced Hypertensive Rats.

In the literature, although there are many studies regarding complications of hypertension, information concerning its influence on visual evoked potentials (VEPs) is limited. This study aims to clarify the possible therapeutic effects of the preferential magnesium (Mg) treatment on VEPs in an experimental hypertension model. Rats were divided into four groups as follows: control, Mg treated (Mg), N(omega)-nitro-L-arginine methyl ester (L-NAME) hypertension, and L-NAME hypertension + Mg treated (L-NAME + Mg). Hypertension was induced by L-NAME which was given to rats orally over 6 weeks (25 mg/kg/day in drinking water). A magnesium-enriched diet (0.8 g/kg) was given to treatment groups for 6 weeks. Systolic blood pressure (SBP) was determined by using the tail-cuff method. Flash VEPs were recorded. Our results revealed that the SBP was significantly increased in the L-NAME group compared to control. Magnesium treatment significantly attenuated SBP in the hypertensive rats compared to the L-NAME group. The mean latencies of P1, N1, P2, N2, and P3 components were significantly prolonged in hypertensive rats compared to control. Treatment with Mg provided a significant decrease in the latencies of P1, N1, P2, N2, and P3 potentials in the L-NAME + Mg group compared to the L-NAME group. Plasma Mg levels were increased in the L-NAME + Mg group compared to the L-NAME group. No change was detected in the Mg levels of the brains in all experimental groups. Magnesium treatment had no effect on the brain nitrate/nitrite and thiobarbituric acid-reactive substances (TBARS) levels in hypertensive rats compared to non-treated rats. There was a positive correlation between the brain TBARS levels and SBP of the rats. The present study suggests that Mg supplementation has the potential to prevent VEP changes in the L-NAME-induced hypertension model.

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.

2.1 GHz electromagnetic field does not change contractility and intracellular Ca2+ transients but decreases ß-adrenergic responsiveness through nitric oxide signaling in rat ventricular myocytes.

PURPOSE: Due to the increasing use of wireless technology in developing countries, particularly mobile phones, the influence of electromagnetic fields (EMF) on biologic systems has become the subject of an intense debate. Therefore, in this study we investigated the effect of 2.1 GHz EMF on contractility and beta-adrenergic (ß-AR) responsiveness of ventricular myocytes. MATERIALS AND METHODS: Rats were randomized to the following groups: Sham rats (SHAM) and rats exposed to 2.1 GHz EMF for 2 h/day for 10 weeks (EM-10). Sarcomere shortening and Ca(2+) transients were recorded in isolated myocytes loaded with Fura2-AM and electrically stimulated at 1 Hz, while L-type Ca(2+) currents (I(CaL)) were measured using whole-cell patch clamping at 36 ± 1°C. Cardiac nitric oxide (NO) levels were measured in tissue samples using a colorimetric assay kit. RESULTS: Fractional shortening and amplitude of the matched Ca(2+) transients were not changed in EM-10 rats. Although the isoproterenol-induced (10(-6) M) I(CaL) response was reduced in rats exposed to EMF, basal I(CaL) density in myocytes was similar between the two groups (p < 0.01). Moreover, EMF exposure led to a significant increase in nitric oxide levels in rat heart (p < 0.02). CONCLUSIONS: Long-term exposure to 2.1 GHz EMF decreases ß-AR responsiveness of ventricular myocytes through NO signaling.

The relationship between oxidative stress markers and visual evoked potentials in different hypertension models.

OBJECTIVE: We aimed to define the influence of different hypertension models on lipid peroxidation markers [conjugated dienes (CD) and thiobarbituric acid-reactive substances (TBARS)], antioxidant protection [paraoxonase-1 (PON1) activity] and visual evoked potential (VEP) changes in rats. METHODS: The study was designed as four different hypertension models. Rats (n=84) were divided equally into six groups: Control group (C), Sham operated (Sham), Two kidney-one clip (2K-1C), One kidney-one clip (1K-1C), Deoxycorticosterone acetate (DOCA) and N-omega-nitro-L-arginine-methyl ester (L-NAME). Brain TBARS, serum lipids (total and lipoprotein bound cholesterols and triglycerides) CD and TBARS levels and PON1 activity were assayed. Comparisons were performed using ANOVA or Wilcoxon/Kruskal-Wallis tests. Pearson correlation and linear regression analysis were used to evaluate associations of independent predictors with hypertension. RESULTS: Mean arterial pressure, brain and serum lipid peroxidation markers, VEP latencies were significantly higher in four hypertensive groups compared with control and sham groups (p<0.05). Compared with controls, PON1 activity was decreased in DOCA, 1K1C and L-NAME groups (p<0.05). Serum PON1 activity was negatively correlated with lipid peroxidation markers and VEPs. In terms of VEP's records linear regression analysis showed that changes in N2 (B=1.51±0.34; p<0.001), P1 (B=-1.71±0.28; p<0.001), P3 (B=0.54±0.14; p<0.001), serum TBARS levels (B=0.94±0.24; p<0.001) and PON1 activity (B=0.05±0.02; p<0.01) were independently associated with elevated blood pressure. CONCLUSION: Lipid peroxidation measured in serum and brain was associated with increased electrophysiological alterations recorded as VEPs. This study might suggest that serum PON1 activity may be protective against brain and serum lipid peroxidation as well as electrophysiological alterations in the brain in different hypertension models.