Neurobehavioural and molecular changes induced by methylmercury exposure during development

Abstract

There is an increasing body of evidence on the possible environmental influence on neurodevelopmental and neurodegenerative disorders. Both experimental and epidemiological studies have demonstrated the distinctive susceptibility of the developing brain to environmental factors such as lead, mercury and polychlorinated biphenyls at levels of exposure that have no detectable effects in adults. Methylmercury (MeHg) has long been known to affect neurodevelopment in both humans and experimental animals. Neurobehavioural effects reported include altered motoric function and memory and learning disabilities. In addition, there is evidence from recent experimental neurodevelopmental studies that MeHg can induce depression-like behaviour. Several mechanisms have been suggested from in vivo- and in vitro-studies, such as effects on neurotransmitter systems, induction of oxidative stress and disruption of microtubules and intracellular calcium homeostasis. Recent in vitro data show that very low levels of MeHg can inhibit neuronal differentiation of neural stem cells. This review summarises what is currently known about the neurodevelopmental effects of MeHg and consider the strength of different experimental approaches to study the effects of environmentally relevant exposure in vivo and in vitro.

Review of the Toxicology of Chlorpyrifos With an Emphasis on Human Exposure and Neurodevelopment

“…Finally, total sample size was smaller in the portion of the cohort born after January 1, 2001; while total sample size was 314, only 77 samples constituted the post-January 1, 2001, subgroup. It is also possible that changes in exposures to other known and suspected neurodevelopmental risks, such as lead, perfluorooctanoic acid (PFOA; Apelberg et al, 2007), methylmercury (Johansson et al, 2007), or any number of environmental factors, might also have contributed to differences in birth outcomes and neurobehavioral measures in these later pregnancies. Thus, although the findings in the Columbia cohort provide support for the hypothesis that chlorpyrifos exposures are associated with adverse neurodevelopmental outcomes, further studies with more rigorous exposure assessment and careful control of other strong confounding factors are needed to clarify this association.…”

Ecophysiology of avian migration in the face of current global hazards

“…Critically, any such increase in circulating toxicants through the mobilization of body stores in migratory birds will coincide with periods requiring both peak aerobic performance (or peak metabolic rate, PMR) and endurance. Finally, even low levels of a number of toxicants have been shown to interfere with memory and learning in humans [64], which suggests that these toxicants may have particular relevance for migratory birds that rely heavily on neurosensory mechanisms to navigate between the various sites along their route.…”

Localizing organomercury uptake and accumulation in zebrafish larvae at the tissue and cellular level

“…Beyond this, however, our knowledge of the mechanisms underlying organic mercury (Hg) toxicity is fragmentary. MeHg-induced changes in cellular Ca 2ϩ have been shown to be important (4)(5)(6)(7), as has oxidative stress (4), and glutamate metabolism (8). In both yeast and human cells, overexpression of the ubiquitin-targeting enzyme Cdc34 confers protection against the cytotoxic effects of MeHg, which leads to the suggestion that an unknown protein containing a signal for ubiquitination by Cdc34 is involved in the development of the cytotoxic effects of MeHg (9)(10)(11).…”