Chronic exposure to an extremely low-frequency magnetic field induces depression-like behavior and corticosterone secretion without enhancement of the hypothalamic-pituitary-adrenal axis in mice.

An extremely low-frequency magnetic field (ELF-MF) is generated by power lines and household electrical devices. Many studies have suggested an association between chronic ELF-MF exposure and anxiety and/or depression. The mechanism of these effects is assumed to be a stress response induced by ELF-MF exposure. However, this mechanism remains controversial. In the present study, we investigated whether chronic ELF-MF exposure (intensity, 1.5 mT; [corrected] total exposure, 200 h) affected emotional behavior and corticosterone synthesis in mice. ELF-MF-treated mice showed a significant increase in total immobility time in a forced swim test and showed latency to enter the light box in a light-dark transition test, compared with sham-treated (control) mice. Corticosterone secretion was significantly high in the ELF-MF-exposed mice; however, no changes were observed in the amount of the adrenocorticotropic hormone and the expression of genes related to stress response. Quantification of the mRNA levels of adrenal corticosteroid synthesis enzymes revealed a significant reduction in Cyp17a1 mRNA in the ELF-MF-exposed mice. Our findings suggest the possibility that high intensity and chronic exposure to ELF-MF induces an increase in corticosterone secretion, along with depression- and/or anxiety-like behavior, without enhancement of the hypothalamic-pituitary-adrenal axis.

Effects of exposure to a time-varying 1.5 T magnetic field on the neurotransmitter-activated increase in intracellular Ca(2+) in relation to actin fiber and mitochondrial functions in bovine adrenal chromaffin cells.

BACKGROUND: It has been reported that exposure to electromagnetic fields influences intracellular signal transduction. We studied the effects of exposure to a time-varying 1.5 T magnetic field on membrane properties, membrane cation transport and intracellular Ca(2+) mobilization in relation to signals. We also studied the mechanism of the effect of exposure to the magnetic field on intracellular Ca(2+) release from Ca(2+) stores in adrenal chromaffin cells. METHODS: We measured the physiological functions of ER, actin protein, and mitochondria with respect to a neurotransmitter-induced increase in Ca(2+) in chromaffin cells exposed to the time-varying 1.5 T magnetic field for 2h. RESULTS: Exposure to the magnetic field significantly reduced the increase in [Ca(2+)]i. The exposure depolarized the mitochondria membrane and lowered oxygen uptake, but did not reduce the intracellular ATP content. Magnetic field-exposure caused a morphological change in intracellular F-actin. F-actin in exposed cells seemed to be less dense than in control cells, but the decrease was smaller than that in cytochalasin D-treated cells. The increase in G-actin (i.e., the decrease in F-actin) due to exposure was recovered by jasplakinolide, but inhibition of Ca(2+) release by the exposure was unaffected. CONCLUSIONS AND GENERAL SIGNIFICANCE: These results suggest that the magnetic field-exposure influenced both the ER and mitochondria, but the inhibition of Ca(2+) release from ER was not due to mitochondria inhibition. The effect of eddy currents induced in the culture medium may indirectly influence intracellular actin and suppress the transient increase in [Ca(2+)]i.

Effects of a time-varying strong magnetic field on transient increase in Ca2+ release induced by cytosolic Ca2+ in cultured pheochromocytoma cells.

Exposure of pheochromocytoma (PC 12) cells to a time-varying 1.51 T magnetic field inhibited an increase in the intracellular Ca2+ concentration ([Ca2+]i) induced by addition of caffeine to Ca(2+)-free medium. This inhibition occurred after a 15-min exposure and was maintained for at least 2 h. [Ca2+]i sharply increased in cells loaded with cyclic ADP-ribose, and 2-h exposure significantly suppressed the increase. Addition of ATP induced a transient increase in intracellular Ca2+ release mediated by IP3 receptor, and this increase was strongly inhibited by the exposure. Results indicated that the magnetic field exposure strongly inhibited Ca2+ release mediated by both IP3 and ryanodine receptors in PC 12 cells. However, thapsigargin-induced Ca2+ influx (capacitative Ca2+ entry) across the cell membrane was unaffected. The ATP content was maintained at the normal level during the 2-h exposure, suggesting that ATP hydrolysis was unchanged. Therefore, Mg2+ which is known to be released by ATP hydrolysis and inhibit intracellular Ca2+ release may not relate the exposure-caused inhibition. Eddy currents induced in culture medium appear to change cell membrane properties and indirectly inhibit Ca2+ release from endoplasmic reticulum and other Ca2+ stores in PC 12 cells.

The retinoic acid receptor agonist Am80 increases hippocampal ADAM10 in aged SAMP8 mice.

The retinoic acid (RA, a vitamin A metabolite) receptor (RAR) is a transcription factor. Vitamin A/RA administration improves the Alzheimer's disease (AD)- and age-related attenuation of memory/learning in mouse models. Recently, a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) was identified as a key molecule in RA-mediated anti-AD mechanisms. We investigated the effect of chronic administration of the RAR agonist Am80 (tamibarotene) on ADAM10 expression in senescence-accelerated mice (SAMP8). Moreover, we estimated changes in the expression of the amyloid precursor protein (APP), amyloid beta (Aß), and hairy/enhancer of split (Hes), which are mediated by ADAM10. Spatial working memory and the levels of a hippocampal proliferation marker (Ki67) were also assessed in these mice. ADAM10 mRNA and protein expression was significantly reduced in the hippocampus of 13-month-old SAMP8 mice; their expression improved significantly after Am80 administration. Further, after Am80 administration, the expression levels of Hes5 and Ki67 were restored and the deterioration of working memory was suppressed, whereas APP and Aß levels remained unchanged. Our results suggest that Am80 administration effectively improves dementia by activating the hippocampal ADAM10-Notch-Hes5 proliferative pathway.

Feed-forward changes in carotid blood flow velocity during active standing.

Orthostatic changes induce temporary loss of circulatory regulation. Feedback systems react to cardiovascular alterations to compensate for the instability. To clarify the existence of anticipatory cardiovascular regulation during active standing, we continuously recorded blood flow velocity (BFV) in the common carotid artery and cerebral blood volume (CBV) in healthy men. The maximum BFV value decreased significantly before standing in the reaction-time condition. The decrease significantly correlated with the change in systolic blood pressure that accompanies upright standing from a supine position. The anticipatory BFV decrease disappeared during self-paced standing, and all BFV parameters significantly declined after the self-paced standing. The CBV recording showed a significant increase in oxyhemoglobin levels before standing in the reaction-time condition. Our study suggests that some feed-forward cardiovascular regulation triggered by central command could be activated before standing, and it may play a functional role in the maintenance of cerebral perfusion during standing.

Retinoic acid receptor antagonist LE540 attenuates wakefulness via the dopamine D1 receptor in mice.

Vitamin A is a common lipophilic vitamin, and its function is mainly mediated by the binding of its metabolite retinoic acid to retinoic acid receptors (RARs) and retinoid X receptors. Recently, it was reported that the expression of the RARb (an RAR subtype) gene determines the contribution of the delta oscillation in the sleep electroencephalogram (EEG) patterns in mice. We also reported that 4-week dietary deficiency of vitamin A (VAD) causes the attenuation of delta power in sleep and spontaneous activity in mice. However, our previous study could not clarify whether the attenuation of delta power by VAD is attributed to the suppression of RARs. To address this problem, we investigated whether the chronic administration of LE540 (30mg/kg/day), an antagonist of RARs, for 1 or 4weeks attenuated EEG delta power during sleep in mice. Consequently, 4-week LE540 administration induced a significant attenuation of wakefulness and delta power in non-rapid eye movement sleep. Western blot analysis revealed a significant decrease in the expression of dopamine D1 receptor (D1DR) in the striatum and tyrosine hydroxylase in the midbrain of mice that were administered LE540 for 4weeks. High-performance liquid chromatography analysis of striatal tissue revealed a significant decrease in the homovanillic acid/dopamine ratio. Meanwhile, dopamine levels did not change in these mice. Our results suggest that the 4-week antagonism of RARs induces the attenuation of delta power. However, the attenuation of delta power may be elicited indirectly by the decrease of wakefulness followed by the hypo-expression of dopamine receptors especially D1DR.

Effects of a 1.5 T time-varying magnetic field on cell volume regulation of bovine adrenal chromaffin cells in hyposmotic media.

Effects of a time-varying magnetic field on cell volume regulation by hyposmotic stress in cultured bovine adrenal chromaffin cells were examined. Through regulatory volume decrease (RVD), cell volume of chromaffin cells that were incubated in a hypotonic medium initially increased, reached a peak and finally recovered to the initial value. Two hour exposure to a magnetic field and addition of cytochalasin D increased peak value and delayed return to initial value. Intracellular F-actin contents initially decreased but returned to normal levels after 10 sec. Two hour exposure to the magnetic field and addition of cytochalasin D continuously reduced the F-actin content. Results suggest that exposure to the magnetic field stimulated disruption of the actin cytoskeleton and that the disruption delayed the recovery to the volume prior to osmotic stress.

Effect of exposure to an extremely low frequency-electromagnetic field on the cellular collagen with respect to signaling pathways in osteoblast-like cells.

The effect of exposure to extremely low frequency-electromagnetic field (ELF-EMF: 3 mT, 60 Hz) on differentiation of mouse osteoblast-like MC3T3-E1 cells was examined together with addition of insulin-like growth factor I (IGF-I). As a marker of the differentiation, the cellular collagen content was determined by the absorbance of Sirius red-stained cells measured at the wavelength of 510-520 nm with an imaging microspectroscopy. Exposure to ELF-EMF increased significantly the collagen in the cells. Treatment with PD98059, an inhibitor of extracellular signal-regulated kinase 1/2 (ERK1/2) activation, reduced the collagen in all of the cells examined on control, IGF-I addition and ELF-EMF exposure, however, PD98059 did not prevent the increase in the collagen caused by ELF-EMF exposure, and IGF-I also increased the collagen in the presence of the inhibitor. When phosphatidylinositol 3-kinase (PI3K) pathway was inhibited by LY294002, the increase in collagen induced by ELF-EMF exposure was accelerated, however, the increase in collagen observed by IGF-I addition was suppressed. Treatment with SB203580, an inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), suppressed the increase in the collagen induced by ELF-EMF exposure, whereas IGF-I addition increased the collagen in the presence of the inhibitor. These results suggested that collagen synthesis stimulated by ELF-EMF exposure was carried out by the participation of p38 MAPK pathway, and that PI3K pathway may have the role to suppress the collagen synthesis induced by ELF-EMF exposure, and that the suppression of the PI3K pathway may allow the acceleration of the collagen synthesis.

Wireless blood velocity spectra measurement system for healthcare evaluation: reference data.

The aim of the present study was to determine the blood velocity and its indices in common carotid artery (CCA) as reference value for clinical and healthcare application using the constructed portable wireless Doppler blood flow velocimeter system. Evaluation of CCA blood velocity waveforms was performed in 202 healthy volunteers in the age range of 20 to 69 years. Multivariate analysis was used to determine the relationship between the fixed factor and the outcome hemodynamic variables after adjustment for the related covariates. Results show a general age-related decrease in flow velocities and change in the velocity waveform. There is also a gender difference in velocity indices, except for peak systolic blood velocity. Gender difference is also found in systolic and pulse blood pressures. The findings suggest that waveform indices provide a more reliable evaluation of effects of aging and gender on CCA flow. In conclusion, normal CCA blood velocity parameters are determined in a total of 202 healthy volunteers between the third and seventh age decade after adjustment for gender and exercise effects. Findings may contribute to improved means of healthcare monitoring and clinical evaluation.

Effect of gender on blood flow velocities and blood pressure: role of body weight and height.

Aging and gender alter arterial hemodynamic function. Gender-related differences in body size may affect the arterial hemodynamics such as systolic blood pressure, wave reflection and pressure wave propagation. To assess the possibility that the differences of carotid blood velocities and brachial blood pressure in women are related to body size, we investigated the arterial hemodynamics in 50 healthy young adults (30 men, 20 women) between the age ranges of 20 to 29 years old. Blood velocities are characterized to 5 components of velocity waveforms as peak systolic (S1), second systolic (S2), incisura between systole and diastole (I), peak diastolic (D) and end-diastolic velocity wave (d). As the most pronounced systolic blood pressure is lower in young women than men (P<0.05). Women have higher diastolic velocity components and second systolic velocity, but have lower systolic velocity compared to men. From that, women have a significant greater wave reflection, smaller vascular resistive and lower vascular elastic recoil than in men. Greater body weight is associated with higher blood pressures (P<0.05) and lower blood velocities (P<0.05). Shorter body height affects not only the increased velocity wave reflection index (r= -0.519, P>0.0001), but also the decrease of peripheral vascular resistive index (RI) and arterial vascular elastic recoil index (r= 0.463, P<0.0001; r= 0.481, P<0.0001, respectively). In conclusion, body size influences blood pressure and velocity regulations in the young population.

Effects of aging and exercise training on the common carotid blood velocities in healthy men.

An age-related alteration in the cardiovascular response to exercise training are evident. The purpose of the study was to investigate the effects of exercise and age on blood velocities in common carotid artery in 82 healthy men between the age ranges of 21 to 67 years old. Blood velocities are characterized to five components of velocity waveforms as peak systolic (S1), second systolic (S2), incisura between systole and diastole (I), peak diastolic (D) and end-diastolic velocity wave (d). Decrease of blood velocities in peak systolic (r= -0.711, P<0.0001) and in peak diastolic velocities (r= -0.521, P<0.0001) with aging are improved and partially restore in particularly older men. The velocity ratio of S2/S2-1 as a reflection index increase with age (r= 0.797, P<0.0001), however is smaller in exercise-trained older compared with sedentary peers. The ratio of 1-I/D as a vascular elastic recoil index decrease with aging (r= -0.640, P<.0001), but is relatively higher in exercise-trained men. Exercise training improves the age-related deterioration in blood velocities and its indices in healthy men. In the further investigations, the assessment of aerobic fitness and vascular aging has potential by using the criteria of peak systolic and peak diastolic, and its indices.

Effects of a time varying strong magnetic field on release of cytosolic free Ca2+ from intracellular stores in cultured bovine adrenal chromaffin cells.

This study was made to explain the mechanisms for the effects of exposure to a time varying 1.51 T magnetic field on the intracellular Ca(2+) signaling pathway. The exposure inhibited an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) in bovine chromaffin cells induced by addition of bradykinin (BK) to a Ca(2+) free medium. The exposure did not change BK induced production of inositol 1,4,5-trisphosphate (IP(3)). [Ca(2+)](i) was markedly increased in IP(3) loaded cells, and this increase was inhibited by the magnetic field exposure. A similar increase in [Ca(2+)](i) by other drugs, which stimulated Ca(2+) release from intracellular Ca(2+) stores, was again inhibited by the same exposure. However, transmembrane Ca(2+) fluxes caused in the presence of thapsigargin were not inhibited by the magnetic field exposure in a Ca(2+) containing medium. Inhibition of the BK induced increase in [Ca(2+)](i) by the exposure for 30 min was mostly recovered 1 h after exposure ended. Our results reveal that the magnetic field exposure inhibits Ca(2+) release from intracellular Ca(2+) stores, but that BK bindings to BK receptors of the cell membrane and intracellular inositol IP(3) production are not influenced.