Changes in the histopathology and in the proteins related to the MAPK pathway in the brains of rats exposed to pre and postnatal radiofrequency radiation over four generations.

The development of new technologies and industry increases the number and variety of electromagnetic field (EMF) sources. Researcher are increasingly interested in the effects of EMF on brain health. The brain's function is largely dependent on electrical excitability, so it would be expected to be vulnerable to EMF. We therefore investigated the effects of brain development in the fetus, histopathological changes in female rats and the hippocampal level of MAPK proteins in male rats after exposed to pre and postnatal 2450 MHz continuous wave (CW) radiofrequency radiation (RFR) over four generations. Four groups; sham, irradiated female, irradiated male, irradiated male and female, with each consisting of four rats (one male and three females) were created. Rats in the exposure groups were whole-body exposed to 2450 MHz CW-RFR for 12 h/day during the experiment. Irradiation started one month before fertilization in the experimental group. On the 18th day of the gestational period, one pregnant rat from each group was decapitated under general anesthesia and the fetuses were taken. The remaining two pregnant rats completed the normal gestation period. When the offspring were two months old, four rats, one male and three female, were allocated for the second generation study. Next generation animals were also experienced the same processes as the first generation rats. This study were evaluated development of brain in fetuses and histopathological changes in brain of female rats using haematoxylin eosin staining, and the hippocampal level of MAPK proteins in brain of male rats by Western Bloting. We observed hemorrhagic areas, irregular cellular localization and vascular structures in the brain of fetal and adult female rat of exposed groups in the all generations. pERK, ptau, pJNK and pP38 were increased in the brain of adult male rat of exposed groups in the all generations (p < 0.005). Pre and postnatal 2450 MHz continuous wave radiofrequency radiation exposure may cause changes in the function of the MAPK pathway affecting cognitive processes such as learning and memory and may cause damage to both the fetus and adult brain tissue. Also, EMF may have potential to affect brain of future generations.

Effects of pre and postnatal 2450 MHz continuous wave (CW) radiofrequency radiation on thymus: Four generation exposure.

This study aims to investigate the effects of pre- and postnatal 2450 MHz continuous wave (CW) radiofrequency radiation (RFR) on the thymus of rats spanning four generations. Four groups; sham, irradiated female, irradiated male, irradiated male and female, each consisting of four rats (one male and three females), were created. During the experiment, rats in the exposure groups were whole-body exposed to 2450 MHz CW-RFR for 12 h/day. Irradiation started one month before the fertilization in the experimental group. When the offspring were two months old, four rats, one male and three female, were allocated for the second-generation study. The remaining offspring were sacrificed under general anesthesia, and their thymuses were removed. The same procedure was applied to the next generation. Two months after the second generation gave birth, third-generation rats were decapitated, and their thymuses were removed. In all groups, cortex, medulla and resident cells could be clearly distinguished in the second and third generations. No differences were observed between the control and two experimental groups, defined as irradiated female and irradiated male. In contrast, vascularization was observed in the thymus of the fourth-generation offspring of the group where both males and females were irradiated. The number of offspring and mass of all rats decreased in the third-generation group. Pre-and postnatal 2450 MHz continuous wave radiofrequency radiation exposure may potentially affect the thymus of future generations.

Age-dependent evaluation of long-term depression responses in hyperthyroid rats: Possible roles of oxidative intracellular redox status.

BACKGROUND: According to the free radical theory, a gradual accumulation of the free radicals normally produced in the body underlies the changes associated with aging. Thyroid hormones (THs) are related to oxidative stress not only due to their stimulation of metabolism but also due to their effects on antioxidant mechanisms. Thyroid dysfunction increases with age; thus, changes in TH levels in elderly individuals could be a factor affecting the development of neurodegenerative diseases. However, the relationship is not always clear, based on current evidence regarding synaptic plasticity. METHODS: Hippocampal long-term depression (LTD) and oxidative status in the hippocampus were evaluated at two different ages (2-3 and 12-14 months) in male rats. Rats were administered 0.2 mg/kg/day of l-thyroxine for 21 days starting at postnatal day 40 to induce hyperthyroidism. LTD was induced in the dentate gyrus using low frequency stimulation of the perforant pathway. Spectrophotometry was performed to measure catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) levels, glutathione peroxidase (GPx) activity, and total nitrite/nitrate (tNOx) and nitric oxide synthase (NOS) levels. RESULTS: A reliable LTD was elicited in young rats with hyperthyroidism, while the same protocol could induce a small magnitude of synaptic LTD in the absence of spike-LTD in control rats. In aged rats, controls did not express LTD, but a significant LTP of spike was induced in the absence of synaptic LTD in hyperthyroid rats. While CAT levels were significantly decreased, MDA levels were increased in the aged groups compared to the corresponding young groups. Young rats with euthyroidism had significantly lower GPx activity than each of the hyperthyroid groups. There was no significant difference in SOD levels among the groups. Compared with aged rats, young rats exhibited a hyperthyroidism-induced decrease in NOS levels. Nevertheless, neither the main effects of age and thyroxine administration nor the interaction between these factors reached significance for tNOx. CONCLUSION: These results indicate that hyperthyroidism-related changes in synaptic plasticity are modulated by aging. This modulation may explain the increased cognitive impairment in this disease at older ages, which probably depends on alterations in NOS levels.

Adult-Onset Hypothyroidism Alters the Metaplastic Properties of Dentate Granule Cells by Decreasing Akt Phosphorylation.

The expression of homosynaptic long-term depression (LTD) governs the subsequent induction of long-term potentiation (LTP) at hippocampal synapses. This process, called metaplasticity, is associated with a transient increase in the levels of several kinases, such as extracellular signal-regulated protein kinases 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and Akt kinase. It has been increasingly realized that the chemical changes in the hippocampus caused by hypothyroidism may be the key underlying causes of the learning deficits, memory loss, and impaired LTP associated with this disease. However, the functional role of thyroid hormones in the "plasticity of synaptic plasticity" has only begun to be elucidated. To address this issue, we sought to determine whether the administration of 6-n-propyl-2-thiouracil (PTU) alters the relationship between priming and the induction of subsequent LTP and related signaling molecules. The activation of ERK1/2, JNK, and Akt was measured in the hippocampus at least 95 min after priming onset. We found that priming stimulation at 5 Hz for 3 s negatively impacted the induction of LTP by subsequent tetanic stimulation in hypothyroid animals, as manifested by a more rapid decrease in the fEPSP slope and population spike amplitude. This phenomenon was accompanied by lower levels of phosphorylated Akt in the surgically removed hippocampus of the hypothyroid rats compared to the euthyroid rats. The metaplastic response and the expression of these proteins in the 1-Hz-primed hippocampus were not different between the two groups. These observations suggest that decreased PI3K/Akt signaling may be involved in the compromised metaplastic regulation of LTP observed in hypothyroidism, which may account for the learning difficulties/cognitive impairments associated with this condition.