Similar incidents occurred in Guatemala, Pakistan, and Ghana (for a review, see Clarkson, 2002). Subsequently, exposure was documented in Iraq where locals consumed bread prepared from seeds treated with a fungicide containing MeHg ( Bakir et al., 1973), causing a large outbreak of human poisoning. Several years later, catastrophic epidemics from environmental MeHg contamination in Japan ( Harada, 1978) and Sweden ( Westöö, 1966) were reported. Human poisoning to MeHg was first reported around 150 years ago in laboratory accidents ( Edwards, 1865). Therefore, fishing communities, which commonly depend greatly on fish for food, can be exposed to toxic levels of MeHg ( Clarkson et al., 2003). As a result of the biomethylation of mercury compounds released mainly from anthropogenic sources in the aquatic environment, MeHg-containing fish represent a major source of human exposure. MeHg is an environmental contaminant that has been shown to cause neurological deficits in both animals and humans ( Clarkson et al., 2003 Farina et al., 2010). Organic mercury compounds, such as methylmercury (MeHg), have been extensively studied because they are able to reach high levels in the central nervous system (CNS), leading to neurotoxic effects ( Aschner et al., 2007 Clarkson and Magos, 2006). The distribution, toxicity and metabolism of mercury are greatly dependent on its chemical form. It exists within the environment in three different chemical forms: elemental mercury vapor, inorganic mercury salts, and organic mercury (Clarkson, 1997).

Mercury (Hg) is present in the environment due to either natural events or anthropogenic sources.

Important chemical contaminants reported to cause neurotoxic effects in humans at environmentally relevant levels of exposure include polychlorinated biphenyls ( Schantz et al., 2003), arsenic ( Wasserman et al., 2004), lead ( Lanphear et al., 2005), manganese ( Takser et al., 2003), pesticides ( Rauh et al., 2006), polycyclic aromatic hydrocarbons ( Perera et al., 2006) and mercury compounds (Grandjean et al., 1997 Debes et al., 2006). Although still debatable, evidence has pointed to a potential link between exposures to chemical contaminants and neurological disorders/mental illness, such as autism ( Landrigan, 2010), Parkinson’s disease ( Barlow et al., 2007), Alzheimer’s disease ( Coppede and Migliore, 2010), amyotrophic lateral sclerosis ( Johnson and Atchison, 2009), just to name a few. Neurological disorders represent an important health concern faced by society, accounting for great numbers of hospitalizations and disabilities ( Schmidt, 2007). These concepts provide the biochemical bases to the understanding of MeHg neurotoxicity, contributing to the discovery of endogenous and exogenous molecules that counteract such toxicity and provide efficacious means for ablating this vicious cycle. The particular sensitivity of the developing brain to MeHg toxicity, the critical role of selenoproteins and the potential protective role of selenocompounds are also discussed. The potential relationship among these events is discussed, with particular emphasis on the neurotoxic cycle triggered by MeHg-induced excitotoxicity and oxidative stress. While the full picture has yet to be unmasked, in vitro approaches based on cultured cells, isolated mitochondria and tissue slices, as well as in vivo studies based mainly on the use of rodents, point to impairment in intracellular calcium homeostasis, alteration of glutamate homeostasis and oxidative stress as important events in MeHg-induced neurotoxicity.

The objective of this mini-review is to summarize data from experimental studies on molecular mechanisms of MeHg-induced neurotoxicity. Although several episodes of MeHg poisoning have contributed to the understanding of the clinical symptoms and histological changes elicited by this neurotoxicant in humans, experimental studies have been pivotal in elucidating the molecular mechanisms that mediate MeHg-induced neurotoxicity. In the aquatic environment, MeHg is accumulated in fish, which represent a major source of human exposure. One of the best known neurotoxins is methylmercury (MeHg), a ubiquitous environmental toxicant that leads to long-lasting neurological and developmental deficits in animals and humans. Although mostly unknown, a few environmental toxicants are recognized causes of neurological disorders and subclinical brain dysfunction. Neurological disorders are common, costly, and can cause enduring disability.

Treatment of mercury poisoning