In Utero Exposure to Methylmercury and Se Deficiency Converge on the Neurobehavioral Outcome in Mice

Watanabe, Chiho; Yin, Kai; Kasanuma, Yuichi; Satoh, Hiroshi

doi:10.1016/s0892-0362(98)00036-1

Cited by 90 publications

(70 citation statements)

References 23 publications

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“…Our results may have some bearing on the "selenium depletion hypothesis" (24), which proposes that mercury compounds scavenge selenium in neurological tissues, causing a local deficiency of essential selenium-dependent enzymes (23,24). This seems plausible because of the potentially limiting transport of selenium to the brain (33).…”

Section: X-ray Fluorescence Imagingmentioning

confidence: 77%

The Chemical Nature of Mercury in Human Brain Following Poisoning or Environmental Exposure

Korbas

O’Donoghue²,

Watson

et al. 2010

ACS Chem. Neurosci.

170

124

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Methylmercury is among the most potentially toxic species to which human populations are exposed, both at high levels through poisonings and at lower levels through consumption of fish and other seafood. However, the molecular mechanisms of methylmercury toxicity in humans remain poorly understood. We used synchrotron X-ray absorption spectroscopy (XAS) to study mercury chemical forms in human brain tissue. Individuals poisoned with high levels of methylmercury species showed elevated cortical selenium with significant proportions of nanoparticulate mercuric selenide plus some inorganic mercury and methylmercury bound to organic sulfur. Individuals with a lifetime of high fish consumption showed much lower levels of mercuric selenide and methylmercury cysteineate. Mercury exposure did not perturb organic selenium levels. These results elucidate a key detoxification pathway in the central nervous system and provide new insights into the appropriate methods for biological monitoring.

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Section: X-ray Fluorescence Imagingmentioning

confidence: 77%

The Chemical Nature of Mercury in Human Brain Following Poisoning or Environmental Exposure

Korbas

O’Donoghue²,

Watson

et al. 2010

ACS Chem. Neurosci.

170

124

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“…Sodium selenite treatment can suppress MeHg-mediated fetotoxicity, neurotoxicity, or developmental toxicity (16 -18). Further, MeHg toxicity was enhanced in selenium-deficient animals (19,20). These reports suggest the possibility that the selenium component of naturally occurring selenium-containing proteins and tRNAs is the protecting factor against MeHg cytotoxicity.…”

Section: Methylmercury (Mehg)mentioning

confidence: 82%

Post-transcriptional Defects of Antioxidant Selenoenzymes Cause Oxidative Stress under Methylmercury Exposure

Usuki¹,

Yamashita

Fujimura

2011

Journal of Biological Chemistry

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Methylmercury (MeHg) toxicity is a continuous environmental problem to human health. The critical role of oxidative stress in the pathogenesis of MeHg cytotoxicity has been clarified, but the molecular mechanisms underlying MeHg-mediated oxidative stress remain to be elucidated. Here we demonstrate a post-transcriptional effect of MeHg on antioxidant selenoenzymes by using a MeHg-susceptible cell line. MeHginduced selenium deficiency leads to failure of the recoding of a UGA codon for selenocysteine and results in degradation of the major antioxidant selenoenzyme glutathione peroxidase 1 (GPx1) mRNA by nonsense-mediated mRNA decay (NMD), a cellular mechanism that detects the premature termination codon (PTC) located 5-upstream of the last exon-exon junction and degrades PTC-containing mRNAs. In contrast, thioredoxin reductase 1 (TrxR1), another antioxidant selenoenzyme of the thioredoxin system, was likely skipped by NMD because of a UGA codon in the last exon. However, TrxR1 activity was decreased despite mRNA up-regulation, which was probably due to the synthesis of aberrant TrxR1 protein without selenocysteine. Changes in selenoenzyme GPx1 and TrxR1 mRNAs were observed earlier than was the incidence of oxidative stress and up-regulation of other antioxidant enzyme mRNAs. Results indicated that the MeHg-induced relative selenium-deficient condition affects the major antioxidant selenoenzymes GPx1 and TrxR1 through a post-transcriptional effect, resulting in the disturbance of cellular redox systems and the incidence of oxidative stress. Treatment with ebselen, a seleno-organic compound, effectively suppressed oxidative stress and protected cells against MeHg-induced relative selenium deficiency and cytotoxicity.

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“…These experimental studies provide an understanding in how Se and MeHg may interact under different exposure regimens. Groups of mice, for example, were given low dietary amounts of Se in a study to investigate the effects of MeHg exposure and in utero Se deficiency on neurobehavior outcome (Watanabe et al, 1999). In a study to examine the concentration of blood and brain MeHg and Se that model the conditions of human exposure more closely, the female rats were exposed to three levels of MeHg and two levels of dietary amounts of Se, with one level at the low end of recommended intakes from laboratory studies .…”

Section: Discussionmentioning

confidence: 99%

“…In a separate study in rats, Ganther et al (1972) showed that MeHg toxicity was decreased by the levels of Se in a diet that were comparable to that was supplied by tuna. In an in utero MeHg and Se study on mice, the group that was given the lowest amount of Se and the highest dose of MeHg was mostly adversely affected in neurobehavioral outcome (Watanabe et al, 1999). A recent study on rodents showed that antioxidant nutrients Se and Vitamin E in a diet may alter MeHg reproductive and developmental toxicity (Beyrouty and Chan, 2006).…”

Section: Introductionmentioning

confidence: 99%

Selenium as a Potential Protective Factor Against Mercury Developmental Neurotoxicity

Choi¹,

Budtz‐Jørgensen²,

Jorgensen³

et al. 2006

Epidemiology

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Experimental studies suggest that selenium (Se) may decrease methylmercury (MeHg) toxicity under certain exposure regimens. In epidemiological studies, the exposure to MeHg occurs from fish and seafood, which are also a source of beneficial nutrients such as selenium. However, little is known about the potential protective effects of dietary Se against MeHg neurotoxicity in humans. The possible interaction was assessed in two birth cohorts in the Faroe Islands, consisting of singleton term births from 1986 to 1987 (N = 1,022), and 1994 to 1995 (N = 182), respectively. Dietary habits in this fishing population included frequent consumption of seafood, including whale meat high in mercury. Both Hg and Se were measured in cord whole blood. Neurodevelopmental outcomes were evaluated at age 7 years in both cohorts, and the smaller cohort also included neurological assessment on several prior occasions. Each outcome was modeled as a function of Hg and Se interactions (with adjustments for potential risk factors) by expressing the effects of log 10 (Hg) within the lowest 25%, the middle 50%, and the highest 25% of the Se distribution. Surplus Se was present in cord blood, the average being a 10-fold molar excess above MeHg. Regression analyses failed to show consistent effects of Se, or statistically significant interaction terms between Se and MeHg. Overall, no evidence was found that Se was an important protective factor against MeHg neurotoxicity. Prevention, therefore, needs to address MeHg exposures rather than Se intakes. Because of the benefits associated with fish intake during pregnancy, consumers should be advised to maintain a high fish and seafood intake that is low in Hg contamination. Additional research is needed to determine the identity of the nutrients responsible for the beneficial effects.

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In Utero Exposure to Methylmercury and Se Deficiency Converge on the Neurobehavioral Outcome in Mice

Cited by 90 publications

References 23 publications

The Chemical Nature of Mercury in Human Brain Following Poisoning or Environmental Exposure

The Chemical Nature of Mercury in Human Brain Following Poisoning or Environmental Exposure

Post-transcriptional Defects of Antioxidant Selenoenzymes Cause Oxidative Stress under Methylmercury Exposure

Selenium as a Potential Protective Factor Against Mercury Developmental Neurotoxicity

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