Methylmercury-Induced Neurotoxicity: Focus on Pro-oxidative Events and Related Consequences

Abstract

Methylmercury (MeHg) is a highly neurotoxic environmental pollutant. Even though molecular mechanisms mediating MeHg toxicity are not completely understood, several lines of evidence indicate that the neurotoxic effects resultant from MeHg exposure represent a consequence of its pro-oxidative properties. In this regard, MeHg is a soft electrophile that preferentially interacts with (and oxidize) nucleophilic groups (mainly thiols and selenols) from biomolecules, including proteins and low-molecular-weight molecules. Such interaction contributes to the occurrence of oxidative stress and impaired function of several molecules [proteins (receptors, transporters, enzymes, structural proteins), lipids (i.e., membrane constituents and intracellular messengers), and nucleic acids (i.e., DNA)], culminating in neurotoxicity.In this chapter, an initial background on the general aspects regarding the neurotoxicology of MeHg, with a particular focus on its pro-oxidative properties and its interaction with nucleophilic thiol- and selenol-containing molecules, is provided. Even though experimental evidence indicates that symptoms (i.e., motor impairment) resultant from MeHg exposure are linked to its pro-oxidative properties, as well as to their molecular consequences (lipid peroxidation, disruption of glutamate and/or calcium homeostasis, etc.), data concerning the relationship between molecular parameters and behavioral impairment others that those related to the motor function (i.e., visual impairment, cognitive skills, etc.) are scarce. Thus, even though scientific research has provided a significant amount of knowledge concerning the mechanisms mediating MeHg-induced neurotoxicity in the last decades, the whole scenario is far from being completely understood, and further research in this area is well warranted.

Inorganic mercury in human astrocytes, oligodendrocytes, corticomotoneurons and the locus ceruleus: implications for multiple sclerosis, neurodegenerative disorders and gliomas

“…Mitochondria are implicated in a number of neurodegenerative diseases and iHg localises to mitochondria (Chang and Hartmann 1972 ). Mercury has a particular affinity for the sulfhydryl groups of cysteine-containing proteins (Clarkson and Magos 2006 ) found in lipid membranes of the Golgi apparatus, the endoplasmic reticulum and lysosomes, all of which have been linked to neurodegenerative diseases (Farina and Aschner 2017 ). Furthermore, ultrastructural studies have shown iHg binds to all these lipid-rich sites in the nervous system (Chang and Hartmann 1972 ).…”

Acute Methylmercury Exposure and the Hypoxia-Inducible Factor-1α Signaling Pathway under Normoxic Conditions in the Rat Brain and Astrocytes in Vitro

“…Methylmercury (MeHg) is a global environmental contaminant targeting the central nervous system (CNS) (Farina and Aschner 2017;Santos et al 2016). Consumption of MeHg-containing fish products (Canuel et al 2006;Carrasco et al 2011;Steuerwald et al 2000;Stopford and Goldwater 1975) and rice (Rothenberg et al 2014;Zhang et al 2010) has been shown to induce neurodegeneration as well as be associated with neurodevelopmental disorders (Belletti et al 2002;Carocci et al 2014;Ceccatelli et al 2010).…”

Oxidative stress accelerates synaptic glutamate dyshomeostasis and NMDARs disorder during methylmercury‐induced neuronal apoptosis in rat cerebral cortex

“…MeHg is one of the environmental accumulative pollutants that could easily pass through the blood‐brain barrier and accumulate in the brain especially in the CNS . The mechanisms of MeHg neurotoxicity have not been fully elucidated, in which oxidative stress and Glu‐mediated excitotoxicity involved may play important roles …”