Biomedical subjects

Mineshi Sakamoto

Publications and source records attributed to Mineshi Sakamoto.

15 recordsLinked to original sources

PubMed2006

Effects of low dose methylmercury administration during the postnatal brain growth spurt in rats.

Male Sprague-Dawley rats from eight litters were orally administered 0.75 mg/kg/day methylmercury (MeHg) chloride from postnatal day (PD) 14 to PD 23. One male pup per litter from eight different litters per treatment group was used. Each pup was used only for a single behavioral test and tested once. The MeHg dose level resulted in Hg brain concentrations of 0.82+/-0.05 microg/g tissue (n=4). Locomotor behavior was studied in the Opto-Varimex apparatus by testing rats (n=8) weekly from PD 24 to PD 45. Performance of rats (n=8) on learning paradigm was analysed on PD 90. MeHg treatment induced a significant reduction in the number of rearings without altering the distance travelled, the resting time and the time spent in the central part of the arena. Results of conditioned avoidance task showed that, unlike control rats, MeHg-treated animals did not show improvement over blocks and never reached a level of performance that would indicate significant learning had taken place. The present results show that low level exposure to MeHg during late brain growth spurt induces subtle and persistent motor and learning deficits, further underlining the serious potential hazard for the exposed children.

Administration, Oral↗

PubMed2006

Effects of mercury vapor exposure on neuromotor function in Chinese miners and smelters.

OBJECTIVES: Current risk assessment of elemental mercury vapor is based on the tremor toxicity. To clarify the neuromotor effects of occupational exposure to mercury vapor, hand tremor and postural sway were measured in 27 miners and smelters (i.e., exposed workers) and 52 unexposed subjects. METHODS: Urine samples were collected and total mercury and creatinine concentrations were determined. Data of the tremor and postural sway were analyzed using the fast Fourier transformation. RESULTS: The geometric means of the urinary mercury level (UHg) were 228 (range 22.6-4,577) microg/g creatinine for the exposed workers and 2.6 (1.0-17.4) microg/g creatinine for the unexposed subjects. Total tremor intensity and frequency-specific tremor intensities at 1-6 and 10-14 Hz were significantly larger in the exposed workers than in the unexposed subjects (P < 0.05), but they were not significantly related to the UHg among the exposed workers (P > 0.05). In contrast, there were no significant differences in any postural sway parameters between the above two groups (P > 0.05), but the transversal sway with eyes open was positively related to the UHg among the exposed workers in using multiple regression analysis (P < 0.05). CONCLUSIONS: These findings suggest that postural sway, as well as hand tremor, may be affected by elemental mercury vapor exposure, but the former test seems to be less sensitive to mercury than the latter one.

Adult↗

PubMed2006

Total mercury levels in hair, toenail, and urine among women free from occupational exposure and their relations to renal tubular function.

To investigate the relations among total mercury levels in hair, toenail, and urine, together with potential effects of methylmercury intake on renal tubular function, we determined their levels, and urinary N-acetyl-beta-D-glucosaminidase activity (NAG) and alpha1-microglobulin (AMG) in 59 women free from occupational exposures, and estimated daily mercury intakes from fish and other seafood using a food frequency questionnaire. Mercury levels (mean+/-SD) in the women were 1.51+/-0.91 microg/g in hair, 0.59+/-0.32 microg/g in toenail, and 0.86+/-0.66 microg/g creatinine in urine; and, there were positive correlations among them (P<0.001). The daily mercury intake of 9.15+/-7.84 microg/day was significantly correlated with total mercury levels in hair, toenail, and urine (r=0.551, 0.537, and 0.604, P<0.001). Among the women, the NAG and AMG were positively correlated with both the daily mercury intake and mercury levels in hair, toenail, and urine (P<0.01); and, these relations were almost similar when using multiple regression analysis to adjust for possible confounders such as urinary cadmium (0.47+/-0.28 microg/g creatinine) and smoking status. In conclusion, mercury resulting from fish consumption can explain total mercury levels in hair, toenail, and urine to some degree (about 30%), partly through the degradation into the inorganic form, and it may confound the renal tubular effect of other nephrotoxic agents. Also, the following equation may be applicable to the population neither with dental amalgam fillings nor with occupational exposures: [hair mercury (microg/g)]=2.44x[toenail mercury (microg/g)].

Adult↗

PubMed2006

Correlations between mercury concentrations in umbilical cord tissue and other biomarkers of fetal exposure to methylmercury in the Japanese population.

Methylmercury (MeHg) is one of the most risky substances to affect humans through fish consumption, and the fetus is known to be in the most susceptible group. Our objective in this study is to examine the relationships of total mercury (THg) and MeHg concentrations between umbilical cord tissue and other tissues as biomarkers of fetal exposure to MeHg in the Japanese population. In total, 116 paired samples were collected in three Japanese districts, the Tsushima Islands, Fukuoka City, and Katsushika ward of metropolitan Tokyo. THg was measured for hair and THg and MeHg were measured in cord tissues, maternal blood, and cord blood. The relationships among tissues in Hg concentrations were similar among districts. Therefore, we analyzed the relationships using all the samples. More than 90% of Hg in cord tissue, cord blood, and maternal blood was MeHg. THg and MeHg in cord blood was about two times higher than in maternal blood. A strong correlation was found between THg and MeHg in cord tissue. The cord tissue THg and MeHg showed a strong correlation with cord blood Hg, which is recognized as the best biomarker for fetal exposure to MeHg. The findings of this study indicate the significance of cord tissue THg and MeHg as biomarkers for fetal exposure to MeHg at parturition.

Adult↗

PubMed2005

Subclinical effects of prenatal methylmercury exposure on cardiac autonomic function in Japanese children.

OBJECTIVES: The subclinical effects of prenatal exposure to methylmercury from fish consumption on the cardiac autonomic function were assessed in 136 Japanese 7-year-old children recruited for this study. METHODS: Samples of child's hair and dry umbilical cord preserved were collected, and hair mercury and cord tissue methylmercury concentrations were determined as current and prenatal exposure biomarkers, respectively. Cardiac autonomic indicators of parasympathetic and sympathetic activities were calculated from the electrocardiographic RR intervals measured. RESULTS: In the children, the cord tissue methylmercury (0.017-0.367, median 0.089 microg/g) was not significantly correlated with the hair mercury (0.43-6.32, median 1.66 microg/g). The cord tissue methylmercury was related negatively to parasympathetic components of cardiac autonomic indicators (P < 0.05) and positively to sympathovagal indices (P < 0.05), even after correction for possible confounders such as age and sex, although the hair mercury was not significantly correlated with any cardiac autonomic indicators. CONCLUSIONS: Despite the potential limitations involved in the retrospective study, these findings suggest that prenatal methylmercury exposure (median of estimated maternal hair mercury at parturition, 2.24 microg/g) may be associated with reduced parasympathetic activity and/or sympathovagal shift.

Animals↗

PubMed2004

Effects of methylmercury on neurodevelopment in Japanese children in relation to the Madeiran study.

OBJECTIVES: A cross-sectional study was carried out to assess the effects of methylmercury exposure on neurodevelopment in Japanese children, in relation to the Madeiran cross-sectional study, and to estimate benchmark dose (BMD) levels using the data of two studies. METHODS: Mercury levels in hair samples obtained from 327 Japanese mothers and their 7-year-old children, and methylmercury levels in the umbilical cord, were determined. Neurodevelopmental examinations, including the brainstem auditory evoked potential (BAEP), were performed on the children. RESULTS: The medians of hair mercury were 1.63 (0.11-6.86) mug/g for mothers and 1.65 (0.35-6.32) mug/g for children, and a significant correlation was seen between the hair mercury levels in mothers and children. The maternal hair mercury was significantly correlated with the methylmercury in the umbilical cords obtained from 49 children. In 210 children whose mothers had not changed their dietary habits since pregnancy, most of the neurodevelopmental variables were not significantly related to hair mercury levels. The BAEP latencies were significantly shorter in the Japanese children than in the 113 Madeiran 7-year-old children, whose mothers had hair mercury of 1.12-54.5 (median 10.9) mug/g. Significant relationships between the maternal hair mercury level and BAEP latencies (peaks III and V, and interpeak I-III) were found only in the merged data of Japanese and Madeiran children. When the lower 95% confidence limit of BMD (BMDL) was calculated, the BMDLs of mercury exposure for BAEP latencies in the merged data were between 6.9 and 10.5 mug/g, and lower than those in the Madeiran children. CONCLUSIONS: It is suggested that Japanese children may ingest similar doses per body weight of methylmercury to their mothers. If maternal hair mercury was used as a proxy for mercury exposure at birth, no significant dose-effect associations with the BAEP latencies were observed in Japanese children with exposure levels below 6.9 mug/g of hair mercury, but only when higher-level exposures from Madeiran children were included. The BMDL was lower for the merged data than for Madeiran children alone.

Adult↗

PubMed2004

Dose-dependent effects of methylmercury administered during neonatal brain spurt in rats.

Rapid brain growth occurs primarily during the third trimester in humans, whereas in rats it occurs after parturition. Therefore, we hypothesized that the effects of methylmercury (MeHg) on the postnatal developing rat nervous system may help in understanding the neurotoxicity on the human fetal brain when the brain is most vulnerable. In the present experiment, the dose-response effects of MeHg treatment during the postnatal developing phase in rats were studied. Male Wistar rats were orally administered 0, 1, 3, and 5 mg/kg/day methylmercury chloride (MMC), respectively, on postnatal day 1 and for 30 consecutive days. The body weight decline began from day 25 and typical symptoms, such as hind-limb crossing and ataxia, were observed in rats treated with 5 mg/kg/day MMC. The weight loss and typical symptoms were not observed in rats treated with 1 and 3 mg/kg/day. Mercury (Hg) concentrations in the brain were 2.6, 4.5, and 9.6 microg/g in the rats treated with 1, 3, and 5 mg/kg/day, respectively, on the day after the final MMC treatment. At 5 to 6 weeks of age, dose-dependent deficits of motor coordination in the rotarod test and learning disability in the passive avoidance response test were observed. Histopathological examination of a proportion of the MeHg-treated rats revealed widespread neuronal degeneration manifested by neuron loss and astrocytosis in the cerebral cortex, striatum, and cerebellum, where severity of the lesions seemed to increase in proportion to the administered dose of MMC. These findings using neonatal rats will be useful for better understanding of the effects of MeHg in the developing human brain during gestation.

Animals↗

PubMed2004

Maternal and fetal mercury and n-3 polyunsaturated fatty acids as a risk and benefit of fish consumption to fetus.

Maternal fish consumption brings both risks and benefits to the fetus from the standpoint of methylmercury (MeHg) and n-3 PUFA (polyunsaturated fatty acids). MeHg is one of the most risky substances to come through fish consumption, and mercury concentrations in red blood cells (RBC-Hg) are the best biomarker of MeHg exposure. Docosahexaenoic acid (DHA, C22:6n-3), which is one of the most important fatty acids for normal brain development and function, is also derived from fish consumption. Our objective in this study was to examine the relationships between RBC-Hg and plasma fatty acid composition in mother and fetus at parturition. Venous blood samples were collected from 63 pairs of mothers and fetuses (umbilical cord blood) at delivery. In all cases, fetal RBC-Hg levels were higher than maternal RBC-Hg levels. The geometric mean of fetal RBC-Hg was 13.4 ng/g, which was significantly (p < 0.01) higher than that of maternal RBC-Hg (8.41 ng/g). While the average fetal/maternal RBC-Hg ratio was 1.6, the individual ratios varied from 1.08 to 2.19, suggesting considerable individual differences in MeHg concentrations between maternal and fetal circulations at delivery. A significant correlation was observed between maternal and fetal DHA concentrations (r = 0.37, p < 0.01). Further, a significant correlation was observed between RBC-Hg and plasma DHA in fetus (r = 0.35, p < 0.01). These results confirm that both MeHg and DHA which originated from fish consumption transferred from maternal to fetal circulation and existed in the fetal circulation with a positive correlation. Pregnant women in particular need not give up eating fish to obtain such benefits. However, they would do well to at least consume smaller fish, which contain less MeHg, thereby balancing the risks and benefits from fish comsumption.

Adolescent↗

PubMed2004

The Tohoku Study of Child Development: A cohort study of effects of perinatal exposures to methylmercury and environmentally persistent organic pollutants on neurobehavioral development in Japanese children.

Several birth cohort studies have shown adverse effects of perinatal exposures to methylmercury (MeHg) and environmentally persistent organic pollutants (POPs). These chemicals are ingested mainly through fish consumption, but little is known about the hazardous effects in Japanese, whose fish consumption is high. The present study, the Tohoku Study of Child Development, was designed to examine the effects of perinatal exposures to MeHg, polychlorinated biphenyls (PCB), dioxins, pesticides, and other chemicals in Japanese children. Six hundred eighty-seven pregnant women were participated in this study with their written informed consent. Maternal peripheral blood, cord blood, cord tissue, placenta, and breast milk samples were collected for chemical analysis. Maternal hair was also taken for MeHg analysis. Infants born at full term were assessed by neurobehavioral tests: the Brazelton Neonatal Behavioral Assessment Scale at three days old, the Kyoto Scale of Psychological Development and the Bayley Scales of Infant Development at 7 and 18 months old, and the Fagan Test of Infant Intelligence at 7 months old. The children will be continuously followed up to ages 6-7 years. Maternal food intake frequency, maternal IQ, socioeconomic status, and home environment were assessed as covariates. The results of this cohort study will allow us to evaluate associations between the neurobehavioral development of children and perinatal exposures to MeHg and environmentally POPs in Japan.

Animals↗

PubMed2004

[Methylmercury].

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Animals↗

PubMed2003

Disruption of postnatal progenitor migration and consequent abnormal pattern of glial distribution in the cerebrum following administration of methylmercury.

Transplacental administration of methylmercury (MeHg) induces disruption of neuronal migration in the developing cerebral cortex. However, the effects of MeHg on glial progenitor migration remain unclear. To understand this, we performed double administration of MeHg and 5-bromo-2-deoxyuridine (BrdU) to neonatal rat pups on postnatal day 2 (P2), when glial cells are generated from progenitors in the subventricular zone (SVZ). Histopathological examination of a proportion of the MeHg-treated rats on P28 revealed no apparent abnormalities of cytoarchitecture or neuron count in either the primary motor or primary somatosensory cortex of the cerebrum. BrdU immunohistochemistry revealed abnormal accumulation of the labeled cells in the deeper layers of the cortices and underlying white matter of both areas, where an excessive number of astrocytes (glial fibrillary acidic protein- or S-100beta-immunolabeled cells) and oligodendrocytes (2',3'-cyclic-nucleotide 3'-phosphohydrolase-labeled cells) were located. Next, to investigate the migration of individual progenitors from the forebrain SVZ of P2 neonates, we labeled them in vivo with a retrovirus encoding green fluorescent protein (GFP), following administration of MeHg, and then examined the distribution pattern of the GFP-labeled cells in the P28 cerebrum. We found that the labeled cells developed into astrocytes and oligodendrocytes and were accumulated abnormally in the lateral white matter as well as in the adjacent deeper layer of the lateral cortex and lateral side of the striatum. Thus, exposure to MeHg in the gliogenic period induced irregular distribution of glia as a consequence of abnormal migration of the postnatal progenitors.

Aging↗

PubMed2003

Estimation of daily mercury intake from seafood in Japanese women: Akita cross-sectional study.

We estimated daily mercury intakes from seafood in 154 mothers residing in several cities and towns in Akita, Japan, to address the relationships between the reference dose (RfD of 0.1 microg/kg body weight per day, derived by US EPA) and daily mercury intakes, combined with hair mercury levels. The frequency and volume of seafood ingested by them were examined using a food frequency questionnaire (FFQ) with 25 kinds of full-scale pictures including fish and shellfish items. Hair mercury concentrations in the mothers were also determined. The geometric means in the mothers were 15.3 (2.65-48.4) microg/day for daily mercury intakes from seafood, calculated on the basis of the references on mercury contents, and 1.73 (0.49-5.82) microg/g for hair mercury concentrations. The daily mercury intake was significantly correlated with hair mercury concentrations (Spearman rank correlation coefficient rs=0.335, p<0.001). No significant differences in mercury intakes were found either between mothers residing in fishing and non-fishing areas or between those in cities and towns (p>0.05). Assuming the methylmercury content rate of 75% in seafood mercury and body weight of 55 kg, the mothers were estimated to ingest methylmercury of 0.21 microg/kg body weight per day. It is suggested that daily mercury intakes, calculated by the FFQ, reflect hair mercury levels, and there is no interregional difference in the daily mercury intake unless any special circumstance exists. Daily methylmercury intake in more than 90% of Japanese women may exceed the RfD, and it therefore seems to be far from the present state of Japanese dietary lives.

Adult↗

PubMed2002

Evaluation of changes in methylmercury accumulation in the developing rat brain and its effects: a study with consecutive and moderate dose exposure throughout gestation and lactation periods.

Methylmercury (MeHg) can be transferred to the fetus through the placenta and to newborn offspring through breast milk. The higher mercury (Hg) accumulation and susceptibility to toxicity in the fetus than in the mother during the gestation period is well known. However, the contribution of MeHg exposure through breast milk to the brain Hg concentration in offspring is not clear. The purposes of this study were to evaluate the changes in Hg concentration in the brain of offspring and its effects on the developing rat brain, based on consecutive and moderate doses of MeHg throughout gestation and lactation. Adult female rats were given a diet containing 5 ppm Hg (as MeHg) for 8 weeks. The administration level was thought not to cause adverse effects in adult rats. The rats were then mated and subsequently given the same diet throughout gestation and after parturition. The newborn offspring were placed with the mothers until postnatal day 30. The offspring were exposed to MeHg throughout their intrauterine life through the placenta, and during the postnatal developing phase via contaminated milk. Furthermore, they were given the same diet containing MeHg for 2 months following weaning. On the day of parturition, the concentration of Hg in the brains of newborns was 1.4 times higher than that in the mothers. During the suckling period the concentration in the brain of the offspring rapidly declined to 1/5 of that at birth, suggesting that MeHg transport by milk was limited while the brain and body volumes increased rapidly. The concentration increased gradually again after the offspring started the contaminated diet. In behavioral tests performed at 5 and 6 weeks of age, MeHg-exposed rats showed a significant deficit in motor coordination in the rotarod test and a learning disability in the passive avoidance response test, compared with controls. Histopathologically, focal cerebellar dysplasia, including the heterotopic location of Purkinje cells and granule cells, was observed. These abnormalities may be induced by the effect of highly accumulated MeHg in the brain during the gestation period. Thus, although offspring are subjected to consecutive and moderate dose MeHg exposure throughout both the gestation and suckling periods, the risk is especially high during gestation but may decrease during lactation.

Animals↗

PubMed2002

Neuronal migration disturbance and consequent cytoarchitecture in the cerebral cortex following transplacental administration of methylmercury.

To understand the effects of methylmercury (MeHg) on neuronal migration in the developing cerebral cortex, we performed double administrations of MeHg and 5-bromo-2-deoxyuridine (BrdU) to pregnant rats on different embryonic days (E11, E13, E16 or E21). Histopathological examination of a proportion of the offspring on postnatal day 28 revealed no apparent cytoarchitectural abnormalities in the primary motor and primary somatosensory cortices of the cerebrum. Morphometric analysis revealed no significant differences in total neuron population in either of these areas, and no differences in subpopulations of cells in any of the cortical layers, between any of the MeHg-exposed groups and the control animals. However, BrdU immunohistochemistry revealed an abnormally widespread distribution of the labeled cells throughout cortical layers II-VI of offspring exposed to MeHg on E16 and E21, indicating disruption of the inside-out pattern of neuronal migration. We examined one aspect of cell-fate determination by applying immunohistochemistry with antibodies against calbindin, parvalbumin, calretinin, and gamma-aminobutyric acid, but found no differences in the topographic distributions of the antibody-labeled cells in the cortex between the controls and the MeHg-exposed offspring. These results suggest that it is the extrinsic circumstances - rather than the timing of neuron generation - that regulates the expression of these proteins.

Animals↗

PubMed2002

Declining risk of methylmercury exposure to infants during lactation.

Methylmercury (MeHg) can be transferred to infants through milk, in addition to passage through the placenta during intrauterine life. The higher MeHg accumulation and susceptibility to toxicity in the fetus than in the mother during the gestation period is well known. However, the contribution of Hg exposure through breast milk to the MeHg concentration in infants is not clear. Our objective in this study was to examine the changes in MeHg levels in infants who were reared on breast milk to evaluate the risks between fetal and breast-feeding periods based on Hg concentrations in red blood cells (RBCs-Hg). RBCs-Hg and plasma-Hg concentrations (Plasma-Hg) in seven pairs of maternal and infant blood samples were compared at birth and 3 months after parturition. RBCs to Plasma-Hg ratio was approximately 8:1 for mothers at parturition and after 3 months, suggesting that their Hg source is MeHg from consumed fish as is general in Japanese. In all seven cases, RBCs-Hg in the umbilical cords were higher than those in the mothers at parturition. The geometric mean of RBCs-Hg in umbilical cords (10.6ng/g) was about 1.4 times higher than that in the mothers (7.1ng/g). There was a strong correlation in RBCs-Hg in mothers and umbilical cords. However, all the infants showed declines in Hg concentrations throughout the breast-feeding period. The geometric mean RBCs-Hg at 3 months of age was 5.8ng/g, accounting for 54% of that in the umbilical cords. Consequently, maternal RBCs-Hg surpassed that of infants at 3 months, opposite to the situation at parturition. The decline in infant RBCs-Hg during the breast-feeding period can be explained by the low Hg transfer through breast milk and the rapid growth of infants after birth. The geometric mean Milk-Hg was low (0.21ng/g), around 20% of that in maternal Plasma-Hg. The average body weight of infants at 3 months increased to about 1.9 times of that at birth. Thus, offspring are subjected to MeHg exposure through both the gestation and the breast-feeding periods; the risk is especially high during gestation but may decrease during breast-feeding.

Adult↗