Effects of methylmercury on the microvasculature of the developing brain.
ABSTRACT The study, undertaken with the aim of further investigating the effects of methylmercury (MeHg) exposure on the developing brain, was performed in the cerebellum of chick embryos, chronically treated with a MeHgCl solution dropped onto the chorioallantoic membrane, and in control embryo cerebella. Quantitative evaluations, performed by cold vapour atomic absorption spectrophotometry, demonstrated a high mercury content in the chorioallantoic membrane, encephalon, liver and kidney of the treated embryos. The morphological observations showed severe neuronal damage consisting of degenerative changes of the granules and Purkinje neurons. The effects on astrocytes were even more severe, since they were extremely rare both in the neuropil and around the vessel wall. Compared with the controls, the cerebellar vessels of MeHg-treated embryos showed immature morphology, poor differentiation of endothelial barrier devices, and high permeability to the exogenous protein horseradish peroxidase. These findings support the hypothesis that MeHg-related neuronal sufferance may be secondary to astrocytic damage and suggest that the developmental neurotoxicity of this compound could also be related to astrocyte loss-dependent impairment of blood-brain barrier (BBB) differentiation.
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ABSTRACT: Humans are exposed to both lead (Pb) and methylmercury (MeHg), two chemicals known to affect the developing nervous system. It is therefore important to know whether these chemicals interact toxicologically to develop reliable estimates of human health risks. The nature of the potential interaction and how it may change with dose are also critical factors which need to be understood and considered in risk assessment. The available toxicological literature was reviewed and yielded five animal studies which involved combined exposure to both metals. None of these studies examined developmental neurotoxicity, the key endpoint of interest. Doses in these studies were also in the range of 1–100 mg kg−1 day−1, which is far above average exposure levels for Pb and MeHg in the U.S. population. The combined exposure literature is therefore uninformative concerning the potential for Pb–MeHg interaction. A subsequent evaluation of the available mechanistic data was conducted, looking for similarities in proposed modes of action relevant at low doses. Shared biological targets suggesting a potential for low dose interaction include protein kinase C, calcium homeostasis, and apoptosis. Whether interaction actually occurs, and the form the interaction might take, remains to be studied. A phased research program is proposed that may provide data needed to address this significant data gap and permit more robust Pb and MeHg risk assessment.Toxicological and Environmental Chemistry 08/2011; 93(7):1423-1462.
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ABSTRACT: Previous studies have shown that combined exposure to ethanol (EtOH) and methylmercury (MeHg) in rats during central nervous system development produces several behavioural impairments. This present study was done to investigate inhibitory avoidance acquisition and panic-like disorders in rats in an elevated T-maze (ETM) model of anxiety. Pregnant rats received tap water or EtOH at 22.5% (w/v) (6.5 g/kg per day, by gavage) during pregnancy and lactation. On the 15th day of pregnancy, half of each group received MeHg (8 mg/kg, by gavage). Adult offspring intoxicated by both EtOH + MeHg showed an increase in the ETM re-exposure time. Upon analysis of the enclosed arms latency in baseline and avoidance 1 session it was observed that the rats spent less time inside the arm, suggesting impairment in their short-term memory. The escape latency decreased for EtOH + MeHg and also for EtOH and MeHg groups, suggesting panic-like behaviour. After 24-h and 7-day trials (tests and retests), MeHg and EtOH + MeHg groups had their latency in the enclosed arm reduced with the exception of the EtOH group, revealing memory impairment. Upon analysis of the risk assessment, animals treated with EtOH + MeHg were the only ones to show a decrease in all evaluation stages. This study demonstrates that the exposure to both EtOH and MeHg has an impact on memory and panic-related behaviours, leading to the assertion that this association of toxicants should be studied more in detail to clarify the precise mechanisms of these pharmacological effects.Behavioural brain research 03/2010; 211(2):191-7. · 3.22 Impact Factor