s involved in cell death. Furthermore, Ca^2+^ stimulates ROS generation by mitochondrial (Farina et al., 2011a).

Mitochondria are one of the target organelle for Hg-induced cell death. Hg decreased mitochondrial transmembrane potential and increased reactive oxygen species (ROS) generation. The changes in mitochondrial membrane potential open the mitochondrial permeability transition pore, which leads to the release of apoptogenic factors, such as cytochrome c, component of the apoptosome that activates caspase cascade. Furthermore, Hg exposure induces a decrease in the activity of enzymes of the mitochondrial energy metabolism such as cytochrome c oxidase, superoxide dismutase and succinate dehydrogenase (do Nascimento et al., 2008).

Several lines of evidence indicate that Hg neurotoxicity is associated with increased levels of reactive (oxygen/nitrogen) species (ROS/RNS). The mechanisms mediating Hg-induced ROS/RNS generation appear to be far more complex. Hg induces a "selenium-deficient-like" condition, which affects glutathione peroxidase (GPx) synthesis and leads to decreased GPx levels, consequently, increased H~2~O~2~ levels. Another mechanism related to the increased H~2~O~2~ levels after Hg exposure appears to be the direct hampering effect of this toxicant toward the entire GSH antioxidant system thus leads to increased levels of brain H~2~O~2~ and lipid peroxidation (Farina et al., 2011b). Lipid peroxidation is the noxious biological event orchestrated by the free radicals such as H~2~O~2~ resulting in structural alterations of membranes and functional impairment of neuronal components.

Moreover, increased intracellular calcium levels are prone to activate neuronal nitric oxide synthase (nNOS), as a result of the overactivation of NMDA-type glutamate receptors, thus increasing nitric oxide (NO) formation. Another interesting and recently reported event that has been connected to the pro-oxidative effects of Hg is the activation of nuclear factor erythroid-2-related factor-2 (Nrf2) (a major regulato