The Catecholaminergic Neurotransmitter System in Methylmercury-Induced Neurotoxicity

Abstract

Figure 1 depicts the synthesis of dopamine and norepinephrine from the non-essential amino acid tyrosine. Within the central nervous system (CNS), dopamine and norepinephrine act as neurotransmitters; the cell groups producing catecholamines are localized in discrete brain regions and project their axon terminals to a wide range of target areas that play important roles in CNS functions (Kobayashi, 2001). Dopaminergic cells are mainly localized in the substantia nigra (A9 cell group) and ventral tegmental area (A10 cell group) (Lindvall et al., 1983). Neurons from the A9 group innervate the caudate-putamen to form the nigrostriatal pathway, which has a pivotal role in motor control (Gerfen,1992). Neurons from the A10 group project their fibers to the nucleus accumbens, amygdala, and prefrontal cortex, forming the mesocorticolimbic pathway, which is involved in emotion, motivation, and memory formation (Le Moal and Simon, 1991). Dopaminergic neurons from the A11-A14 groups are present in the mediobasal region of the hypothalamus, projecting their fibers to the median eminence and pituitary gland (Moore and Lookingland, 1995), modulating pituitary gland function. Farina et al.

Neurodevelopmental Effects of Mercury

“…There is an large number of studies corroborating the inhibitory effect of E + Hg in thiolcontaining proteins (Farina et al 2017; some examples are listed in Table 3). Among them, are neurotransmitter receptors, various enzymes and cation channels (Farina et al 2017).…”

“…There is an large number of studies corroborating the inhibitory effect of E + Hg in thiolcontaining proteins (Farina et al 2017; some examples are listed in Table 3). Among them, are neurotransmitter receptors, various enzymes and cation channels (Farina et al 2017). However, the question of concentration, distribution and reactivity of cysteinyl residues in thiol-containing proteins is also a critical point and serious limitation in understanding the neurotoxicity of E + Hg forms.…”

Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leading to impairment of learning and memory

“…As corollary, the occurrence of free MeHg and Hg2+ or bound to other ligands such as carboxylates, amines, chloride or hydroxyl anions in the physiological media of living cells is insignificant or nonexistent (George et al 2008). The binding of MeHg to abundant low molecular mass thiols or LMM-SH (e.g., cysteine and reduced glutathione-GSH) and high molecular mass thiol-containing proteins or HMM-SH (e.g., albumin, hemoglobin, etc) is critical for the MeHg distribution from non-target to target organs and cells (Farina et al 2017). The coordination of MeHg with one -S-group of a LMM-SH will determine MeHg distribution to its targets organs, including the brain.…”

“…conjugates) to a free thiol/thiolate-or selenol/selenolate-group from non-target or target proteins. Thus, the interaction of MeHg with its target proteins in the brain usually involves the exchange of MeHg from low-molecular mass conjugates (LMM-S-conjugates) to a thiol or selenol group in different types of proteins (Rabenstein 1978b;Rabenstein and Fairhurst, 1975;Reid and Rabenstein et al;1982;Rabenstein and Reid, 1984;Farina et al 2011Farina et al , 2017Dórea et al 2013).  31…”

Cellular and Molecular Mechanisms Mediating Methylmercury Neurotoxicity and Neuroinflammation

“…Even though GABAergic, dopaminergic, and cholinergic neurotransmission has been pointed as potential targets of MeHg toxicity, the most available data concerning neurotoxic effect of MeHg implies the glutamate neurotransmitter system [ 211 , 212 ].…”