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.

Frontal EEG alterations induced by hippocampal amyloid pathology in rats.

PURPOSE: In this study, it was aimed to determine the dose-dependent effects of hippocampal amyloid beta (Aß) on frontal EEG activity and to elucidate the possible non-invasive biomarkers by recording spontaneous EEG in free-moving rats. MATERIAL AND METHODS: Male albino Wistar rats aged 3 months were randomly divided into 4 groups (n â€‹= â€‹8 for each group), obtained by intrahippocampal injection of saline or different doses of Aß1-42 i.e. 0.01 â€‹µg/µl, 0.1 â€‹µg/µl, and 1 â€‹µg/µl. After two weeks of recovery period, spontaneous EEG recordings were obtained from frontal regions and spectral power analyses were performed. RESULTS: We detected a general slowdown in the brain activity two weeks after Aß1-42 injection. We observed significant increases in frontal alpha power (p â€‹= â€‹0.0021) and significant decreases in frontal beta power (p â€‹= â€‹0.0003) between the Sh and Aß1-42-injected groups. More specifically, the ratio of the frontal EEG beta and alpha power (rFBA) was significantly affected by the intrahippocampal injection of Aß1-42 (p â€‹< â€‹0.0001). Also, we observed that rFBA was negatively and strongly correlated with hippocampal Aß1-42 peptide levels (r â€‹= â€‹-0.781, p â€‹< â€‹0.0001). CONCLUSION: Our findings indicate that spontaneous frontal EEG beta and alpha activity were significantly affected by the intrahippocampal injection of Aß1-42. However, the results suggest that the power ratios of these bands are more sensitive to the hippocampal amyloid pathology. As such, it is proposed that the rFBA may be a more effective biomarker for diagnosing hippocampal pathology induced by Aß1-42.

The Role of Ryanodine Receptors in Regulating Neuronal Activity and Its Connection to the Development of Alzheimer's Disease.

Research into the early impacts of Alzheimer's disease (AD) on synapse function is one of the most promising approaches to finding a treatment. In this context, we have recently demonstrated that the Abeta42 peptide, which builds up in the brain during the processing of the amyloid precursor protein (APP), targets the ryanodine receptors (RyRs) of mouse hippocampal neurons and potentiates calcium (Ca2+) release from the endoplasmic reticulum (ER). The uncontrolled increase in intracellular calcium concentration ([Ca2+]i), leading to the development of Ca2+ dysregulation events and related excitable and synaptic dysfunctions, is a consolidated hallmark of AD onset and possibly other neurodegenerative diseases. Since RyRs contribute to increasing [Ca2+]i and are thought to be a promising target for AD treatment, the goal of this review is to summarize the current level of knowledge regarding the involvement of RyRs in governing neuronal function both in physiological conditions and during the onset of AD.

Two firing modes and well-resolved Na+, K+, and Ca2+ currents at the cell-microelectrode junction of spontaneously active rat chromaffin cell on MEAs.

We recorded spontaneous extracellular action potentials (eAPs) from rat chromaffin cells (CCs) at 37 °C using microelectrode arrays (MEAs) and compared them with intracellularly recorded APs (iAPs) through conventional patch clamp recordings at 22 °C. We show the existence of two distinct firing modes on MEAs: a ~ 4 Hz irregular continuous firing and a frequent intermittent firing mode where periods of high-intraburst frequency (~ 8 Hz) of ~ 7 s duration are interrupted by silent periods of ~ 12 s. eAPs occurred either as negative- or positive-going signals depending on the contact between cell and microelectrode: either predominantly controlled by junction-membrane ion channels (negative-going) or capacitive/ohmic coupling (positive-going). Negative-going eAPs were found to represent the trajectory of the Na+, Ca2+, and K+ currents passing through the cell area in tight contact with the microelectrode during an AP (point-contact junction). The inward Nav component of eAPs was blocked by TTX in a dose-dependent manner (IC50 ~ 10 nM) while the outward component was strongly attenuated by the BK channel blocker paxilline (200 nM) or TEA (5 mM). The SK channel blocker apamin (200 nM) had no effect on eAPs. Inward Nav and Cav currents were well-resolved after block of Kv and BK channels or in cells showing no evident outward K+ currents. Unexpectedly, on the same type of cells, we could also resolve inward L-type currents after adding nifedipine (3 µM). In conclusion, MEAs provide a direct way to record different firing modes of rat CCs and to estimate the Na+, Ca2+, and K+ currents that sustain cell firing and spontaneous catecholamines secretion.

Cochlear pathology in preeclamptic rats: protective effects of vitamin D and magnesium sulfate.

Background/aim: This study investigated the possible degeneration in cochlear morphology induced by preeclampsia (PE) and the therapeutic/preventive effect of vitamin D (Vit D) and magnesium sulfate (MgSO4) used separately and together on feto-maternal outcomes. Materials and methods: We created PE in rats using a reduced uterine perfusion pressure (RUPP) animal model and recorded blood pressure (BP), embryonic survival (ES), and embryonic weight (EW) and evaluated cochlear morphology by electron microscopy. Results: The PE group had elevated BP, a decreased number and weight of live pups, and significant degeneration in the cochlea compared to the sham group. In the PEV group, we observed significant beneficial effects of Vit D supplementation at 14.5 and 19.5 dpc in terms of BP (p < 0.05), EW (p < 0.001), and cochlear degeneration compared to the PE group. In the PEM group, BP (p < 0.05) and cochlear degeneration nearly reached the level found in the sham group. However, although the EW was statistically different in the PE group, it did not reach sham group levels. We also observed that BP returned to sham level (p < 0.01) and noticed significant increases in the EW (p < 0.0001) and ES (p = 0.017) in the PEMV group compared to the PE group. According to the scanning electron microscope results, combined administration of VitD and MgSO4 is more effective than separate administration in improving cochlear degeneration induced by PE. Conclusion: The administration of Vit D and MgSO4 during pregnancy has beneficial effects on PE pathology and may play a significant role in preventing PE-related complications, including cochlear degeneration.

Loss of ARHGAP15 affects the directional control of migrating interneurons in the embryonic cortex and increases susceptibility to epilepsy.

GTPases of the Rho family are components of signaling pathways linking extracellular signals to the control of cytoskeleton dynamics. Among these, RAC1 plays key roles during brain development, ranging from neuronal migration to neuritogenesis, synaptogenesis, and plasticity. RAC1 activity is positively and negatively controlled by guanine nucleotide exchange factors (GEFs), guanosine nucleotide dissociation inhibitors (GDIs), and GTPase-activating proteins (GAPs), but the specific role of each regulator in vivo is poorly known. ARHGAP15 is a RAC1-specific GAP expressed during development in a fraction of migrating cortical interneurons (CINs) and in the majority of adult CINs. During development, loss of ARHGAP15 causes altered directionality of the leading process of tangentially migrating CINs, along with altered morphology in vitro. Likewise, time-lapse imaging of embryonic CINs revealed a poorly coordinated directional control during radial migration, possibly due to a hyper-exploratory behavior. In the adult cortex, the observed defects lead to subtle alteration in the distribution of CALB2-, SST-, and VIP-positive interneurons. Adult Arhgap15-knock-out mice also show reduced CINs intrinsic excitability, spontaneous subclinical seizures, and increased susceptibility to the pro-epileptic drug pilocarpine. These results indicate that ARHGAP15 imposes a fine negative regulation on RAC1 that is required for morphological maturation and directional control during CIN migration, with consequences on their laminar distribution and inhibitory function.

The ryanodine receptor-calstabin interaction stabilizer S107 protects hippocampal neurons from GABAergic synaptic alterations induced by Abeta42 oligomers.

The oligomeric form of the peptide amyloid beta 42 (Abeta42) contributes to the development of synaptic abnormalities and cognitive impairments associated with Alzheimer's disease (AD). To date, there is a gap in knowledge regarding how Abeta42 alters the elementary parameters of GABAergic synaptic function. Here we found that Abeta42 increased the frequency and amplitude of miniature GABAergic currents as well as the amplitude of evoked inhibitory postsynaptic currents. When we focused on paired pulse depression (PPD) to establish whether GABA release probability was affected by Abeta42, we did not observe any significant change. On the other hand, a more detailed investigation of the presynaptic effects induced by Abeta42 by means of multiple probability fluctuation analysis and cumulative amplitude analysis showed an increase in both the size of the readily releasable pool responsible for synchronous release and the number of release sites. We further explored whether ryanodine receptors (RyRs) contributed to exacerbating these changes by stabilizing the interaction between RyRs and the accessory protein calstabin. We observed that the RyR-calstabin interaction stabilizer S107 restored the synaptic parameters to values comparable to those measured in control conditions. In conclusion, our results clarify the mechanisms of potentiation of GABAergic synapses induced by Abeta42. We further suggest that RyRs are involved in the control of synaptic activity during the early stage of AD onset and that their stabilization could represent a new therapeutical approach for AD treatment. KEY POINTS: Accumulation of the peptide amyloid beta 42 (Abeta42) is a key characteristic of Alzheimer's disease (AD) and causes synaptic dysfunctions. To date, the effects of Abeta42 accumulation on GABAergic synapses are poorly understood. The findings reported here suggest that, similarly to what is observed on glutamatergic synapses, Abeta42 modifies GABAergic synapses by targeting ryanodine receptors and causing calcium dysregulation. The GABAergic impairments can be restored by the ryanodine receptor-calstabin interaction stabilizer S107. Based on this research, RyRs stabilization may represent a novel pharmaceutical strategy for preventing or delaying AD.

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.

Investigation of the effects of trophectoderm morphology on obstetric outcomes in fifth day blastocyst transfer in patients undergoing in-vitro-fertilization

Objective: Trophectoderm (TE) cells are the first differentiating cells in embryo development and have epithelial features. TE cells, which associate with implantation of the blastocyst into the uterine endometrium, contribute to the formation of the placenta. Inner cells mass (ICM) together with TE cells are used for determining embryo quality. The aim of this study was to investigate the role of TE and ICM cells on pregnancy outcome in 5th day blastocyst transferred in-vitro-fertilization (IVF) pregnancy. Material and Methods: This was a retrospective study using data from all patients who applied for blastocyst transfer IVF between January 2015 and March 2019 at the Reproductive Endocrinology and Infertility Center of Akdeniz University Faculty of Medicine, Department of Obstetrics and Gynecology. ALPHA Istanbul consensus evaluation system was used for grading of the blastocyst. The embryo quality, expansion, ICM and TE morphology of the 5th day transferred blastocyst was assessed, together with abortion rate, live birth rate, pregnancy complications, and pregnancy outcomes. Results: There was a significantly increased risk of preeclampsia (PE) (7.8% vs 1.1%; p=0.041), preterm delivery (PD) (36% vs 17.7%; p=0.037), and antenatal bleeding rates (13.6% vs 5%; p=0.021) in TE-C compared to the TE-A + TE-B blastocysts. Furthermore, a higher rate of obstetric complications was observed in ICM-C compared to ICM-A and B (p=0.003). There was a significant correlation between TE morphology and implantation success, ongoing pregnancy rate, and abortion incidence. Conclusion: These results suggest that TE cell morphology is related to implantation success and pregnancy outcomes, especially in terms of the risk of abortion, PE, PD, and antenatal bleeding. It may be advisable to counsel women concerning possible poor obstetric outcome due to poor ICM quality. Future prospective and controlled studies are needed to clarify this association.

Alleviation of prilocaine-induced epileptiform activity and cardiotoxicity by thymoquinone.

PURPOSE: This study investigated whether thymoquinone (TQ) could alleviate central nervous system (CNS) and cardiovascular toxicity of prilocaine, a commonly used local anesthetic. METHODS: Rats were randomized to the following groups: control, prilocaine treated, TQ treated and prilocaine + TQ treated. Electroencephalography and electrocardiography electrodes were placed and trachea was intubated. Mechanical ventilation was initiated, right femoral artery was cannulated for continuous blood pressure measurements and blood-gas sampling while the left femoral vein was cannulated for prilocaine infusion. Markers of myocardial injury, reactive oxygen/nitrogen species (ROS/RNS) generation and total antioxidant capacity (TAC) were assayed by standard kits. Aquaporin-4 (AQP4), nuclear factor(NF)κB-p65 and -p50 subunit in brain tissue were evaluated by histological scoring. RESULTS: Blood pH and partial oxygen pressure, was significantly decreased after prilocaine infusion. The decrease in blood pH was alleviated in the prilocaine + TQ treated group. Prilocaine produced seizure activity, cardiac arrhythmia and asystole at significantly lower doses compared to prilocaine + TQ treated rats. Thymoquinone administration attenuated levels of myocardial injury induced by prilocaine. Prilocaine treatment caused increased ROS/RNS formation and decreased TAC in heart and brain tissue. Thymoquinone increased heart and brain TAC and decreased ROS/RNS formation in prilocaine treated rats. AQP4, NFκB-p65 and NFκB-p50 expressions were increased in cerebellum, cerebral cortex, choroid plexus and thalamic nucleus in prilocaine treated rats. Thymoquinone, decreased the expression of AQP4, NFκB-p65 and NFκB-p50 in brain tissue in prilocaine + TQ treated rats. CONCLUSION: Results indicate that TQ could ameliorate prilocaine-induced CNS and cardiovascular toxicity.

Cav1.2 channelopathies causing autism: new hallmarks on Timothy syndrome.

Cav1.2 L-type calcium channels play key roles in long-term synaptic plasticity, sensory transduction, muscle contraction, and hormone release. De novo mutations in the gene encoding Cav1.2 (CACNA1C) causes two forms of Timothy syndrome (TS1, TS2), characterized by a multisystem disorder inclusive of cardiac arrhythmias, long QT, autism, and adrenal gland dysfunction. In both TS1 and TS2, the missense mutation G406R is on the alternatively spliced exon 8 and 8A coding for the IS6-helix of Cav1.2 and is responsible for the penetrant form of autism in most TS individuals. The mutation causes specific gain-of-function changes to Cav1.2 channel gating: a "leftward shift" of voltage-dependent activation, reduced voltage-dependent inactivation, and a "leftward shift" of steady-state inactivation. How this occurs and how Cav1.2 gating changes alter neuronal firing and synaptic plasticity is still largely unexplained. Trying to better understanding the molecular basis of Cav1.2 gating dysfunctions leading to autism, here, we will present and discuss the properties of recently reported typical and atypical TS phenotypes and the effective gating changes exhibited by missense mutations associated with long QTs without extracardiac symptoms, unrelated to TS. We will also discuss new emerging views achieved from using iPSCs-derived neurons and the newly available autistic TS2-neo mouse model, both appearing promising for understanding neuronal mistuning in autistic TS patients. We will also analyze and describe recent proposals of molecular pathways that might explain mistuned Ca2+-mediated and Ca2+-independent excitation-transcription signals to the nucleus. Briefly, we will also discuss possible pharmacological approaches to treat autism associated with L-type channelopathies.

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.

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.

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.