Comparative effects of methylmercury on parallel-fiber and climbing-fiber responses of rat cerebellar slices. (1/572)

The environmental neurotoxicant methylmercury (MeHg) causes profound disruption of cerebellar function. Previous studies have shown that acute exposure to MeHg impairs synaptic transmission in both the peripheral and central nervous systems. However, the effects of MeHg on cerebellar synaptic function have never been examined. In the present study, effects of acute exposure to MeHg on synaptic transmission between parallel fibers or climbing fibers and Purkinje cells were compared in 300- to 350-microm cerebellar slices by using extracellular and intracellular microelectrode-recording techniques. Field potentials of parallel-fiber volleys (PFVs) and the associated postsynaptic responses (PSRs) were recorded in the molecular layer by stimulating the parallel fibers in transverse cerebellar slices. The climbing-fiber responses were also recorded in the molecular layer by stimulating white matter in sagittal cerebellar slices. At 20, 100, and 500 microM, MeHg reduced the amplitude of both PFVs and the associated PSRs to complete block, however, it blocked PSRs more rapidly than PFVs. MeHg also decreased the amplitudes of climbing-fiber responses to complete block. For all responses, an initial increase in amplitude preceded MeHg-induced suppression. Intracellular recordings of excitatory postsynaptic potentials of Purkinje cells were compared before and after MeHg. At 100 microM and 20 microM, MeHg blocked the Na+-dependent, fast somatic spikes and Ca++-dependent, slow dendritic spike bursts. MeHg also hyperpolarized and then depolarized Purkinje cell membranes, suppressed current conduction from parallel fibers or climbing fibers to dendrites of Purkinje cells, and blocked synaptically activated local responses. MeHg switched the pattern of repetitive firing of Purkinje cells generated spontaneously or by depolarizing current injection at Purkinje cell soma from predominantly Na+-dependent, fast somatic spikes to predominantly Ca++-dependent, low amplitude, slow dendritic spike bursts. Thus, acute exposure to MeHg causes a complex pattern of effects on cerebellar synaptic transmission, with apparent actions on both neuronal excitability and chemical synaptic transmission.  (+info)

Biotransformation of methylmercury in vitro. (2/572)

Inorganic mercury formation from methylmercury by the mouse liver and kidney was studied in vitro. With chopped liver or kidney, inorganic mercury was formed from added methylmercury, but when the tissue was homogenized, the activity was diminished. Equimolar addition of selenium had no effect on the reaction.  (+info)

The effect of prenatal methylmercury exposure on the GSH level and lipid peroxidation in the fetal brain and placenta of mice. (3/572)

Effect of prenatal exposure to methylmercury (MeHg) on the glutathione (GSH) levels and lipid peroxidation in the fetal brain was examined. Pregnant ICR mice were injected with 3 mgHg/kg of MeHg on gestational day 12, 13 and 14 (G12-14). On the G14 or G17, the fetal brains were removed and their GSH levels and thiobarbituric acid-reactive substances (TBARS) levels were determined. On the G17, GSH level of MeHg-treated fetal brain was significantly higher than that of the control brain; the TBARS level showed the similar trend but the difference was not significant. These results indicated that the prenatal MeHg treatment disturbed the normal GSH level in the fetal brain and warranted further investigation on the significance of this GSH perturbation.  (+info)

Phytoremediation of methylmercury pollution: merB expression in Arabidopsis thaliana confers resistance to organomercurials. (4/572)

Methylmercury is an environmental toxicant that biomagnifies and causes severe neurological degeneration in animals. It is produced by bacteria in soils and sediments that have been contaminated with mercury. To explore the potential of plants to extract and detoxify this chemical, we engineered a model plant, Arabidopsis thaliana, to express a modified bacterial gene, merBpe, encoding organomercurial lyase (MerB) under control of a plant promoter. MerB catalyzes the protonolysis of the carbon---mercury bond, removing the organic ligand and releasing Hg(II), a less mobile mercury species. Transgenic plants expressing merBpe grew vigorously on a wide range of concentrations of monomethylmercuric chloride and phenylmercuric acetate. Plants lacking the merBpe gene were severely inhibited or died at the same organomercurial concentrations. Six independently isolated transgenic lines produced merBpe mRNA and MerB protein at levels that varied over a 10- to 15-fold range, and even the lowest levels of merBpe expression conferred resistance to organomercurials. Our work suggests that native macrophytes (e.g., trees, shrubs, grasses) engineered to express merBpe may be used to degrade methylmercury at polluted sites and sequester Hg(II) for later removal.  (+info)

Activated human T lymphocytes exhibit reduced susceptibility to methylmercury chloride-induced apoptosis. (5/572)

Mercurials have been shown to cause apoptosis in human T cells. The objective of this study was to evaluate and compare the relative susceptibility of resting versus activated T cells to methyl mercury chloride (MeHgCl)-induced cell death. Apoptosis was assessed by Hoechst 33258 and 7-AAD staining and annexin V binding. Our results show that activation of T cells by PHA, PMA, and ionomycin, or IL-2, reduces mercury-induced apoptosis by approximately 50%. We have previously shown that the underlying basis for these toxic effects involves perturbation of mitochondrial function leading to oxidative stress and the release of cytochrome c to the cytosol. Therefore, the ability of MeHgCl to alter the mitochondrial transmembrane potential (delta psi m) and to induce the generation of reactive oxygen species (ROS) was evaluated in activated T-cells. Both resting and activated cells treated with MeHgCl exhibited a decrease in delta psi m when compared to respective control cells. ROS production was elevated in resting cells following treatment with mercury; in contrast, fewer activated T cells exhibit increased levels of ROS in the presence of MeHgCl. Similarly, MeHgCl treatment resulted in the release of cytochrome c to the cytoplasm in non-activated T cells but failed to do so in the activated population. These results lead us to examine intracellular levels of bcl-2, a protein that has been shown to regulate apoptosis, presumably via its ability to associate with the mitochondrial membrane. Bcl-2 levels were found, in resting cells, to be low in the presence or absence of mercury. In comparison, activated T cells expressed elevated levels of bcl-2. The relationship between mercury-induced apoptosis in human T cells, mitochondrial dysfunction, and intracellular levels of bcl-2 are discussed.  (+info)

Methylmercury neurotoxicity in Amazonian children downstream from gold mining. (6/572)

In widespread informal gold mining in the Amazon Basin, mercury is used to capture the gold particles as amalgam. Releases of mercury to the environment have resulted in the contamination of freshwater fish with methylmercury. In four comparable Amazonian communities, we examined 351 of 420 eligible children between 7 and 12 years of age. In three Tapajos villages with the highest exposures, more than 80% of 246 children had hair-mercury concentrations above 10 microg/g, a limit above which adverse effects on brain development are likely to occur. Neuropsychological tests of motor function, attention, and visuospatial performance showed decrements associated with the hair-mercury concentrations. Especially on the Santa Ana form board and the Stanford-Binet copying tests, similar associations were also apparent in the 105 children from the village with the lowest exposures, where all but two children had hair-mercury concentrations below 10 microg/g. Although average exposure levels may not have changed during recent years, prenatal exposure levels are unknown, and exact dose relationships cannot be generated from this cross-sectional study. However, the current mercury pollution seems sufficiently severe to cause adverse effects on brain development.  (+info)

Methylmercury exposure biomarkers as indicators of neurotoxicity in children aged 7 years. (7/572)

The mercury concentration in blood or scalp hair has been widely used as a biomarker for methylmercury exposure. Because of the increased risks associated with exposures during prenatal and early postnatal development, biomarker results must be interpreted with regard to the age-dependent susceptibility. The authors compared regression coefficients for five sets of exposure biomarkers in 917 children from the Faroe Islands examined at birth, 1 year, and 7 years. Outcome variables were the results of neuropsychologic examination carried out in 1993-1994 at age 7 years. After adjustment for covariates, the cord-blood concentration showed the clearest associations with deficits in language, attention, and memory. Fine-motor function deficits were particularly associated with the maternal hair mercury at parturition. Mercury concentrations in the child's blood and hair at age 7 years were significant predictors only of performance on memory for visuospatial information. These findings emphasize the usefulness of the cord-blood mercury concentration as a main risk indicator. They also support the notion that the greatest susceptibility to methylmercury neurotoxicity occurs during late gestation, while early postnatal vulnerability is less, and they suggest that the time-dependent susceptibility may vary for different brain functions.  (+info)

Blood and brain mercury levels after chronic gestational exposure to methylmercury in rats. (8/572)

Female rats were exposed to 0, 0.5, or 6 ppm Hg (as methylmercuric chloride, 10 rats/group) in drinking water. For half the rats, exposure began 4 weeks before mating and for the others, exposure began 7 weeks before mating. All mating was done with an unexposed male. Maternal exposure continued to post-natal day (PN) 16. Blood and whole-brain mercury concentrations were determined in pups on PN 0 (birth) and PN 21 (weaning). Maternal water consumption was monitored daily during gestation and lactation. Maternal water consumption increased 2- to 3-fold through gestation for all groups. Mercury levels in blood and brain were unrelated to the duration of exposure before mating, although reproductive success appeared to be so related. Mercury levels in both media were closely related to consumption during gestation, but apparently maternal exposure during lactation did not result in exposure to the nursing pups. Brain mercury in offspring decreased between birth and weaning from 0.49 to 0.045 ppm in the low-dose rats and from 9.8 to 0.53 ppm in the high-dose rats. The brain increased in weight only about 5.5-fold during this time, indicating that there was minimal mercury exposure and some net loss from brain during this period. Brain:blood ratios averaged about 0.14 at birth and 0.24 at weaning, suggesting differential loss from neural and non-neural tissue. These ratios are higher than those reported in studies using less chronic exposure conditions or with adult rats. Brain concentrations of mercury in females in the low-dose group were about 10-15% higher than those seen in their male siblings. At the higher dose, the males had slightly higher levels of mercury in the brain than did their female siblings at birth. The relationship between brain concentration (in ppm) and cumulative mercury consumption, also expressed on a ppm basis (cumulative mercury consumed divided by maternal body weight at parturition), was not linear but was well described by a power-function relationship: Hg = A*(cum exposure)b where the exponent, b, was 1.12 and 1.17 for blood and brain, respectively, at birth. This exponent was indistinguishable from 1.0 for both media at weaning, indicating that the relationship between exposure and blood and brain levels became linear.  (+info)