Abstract
Environmental exposure to arsenic (As), lead (Pb), and cadmium (Cd) frequently occurs; however, data on the specific effects of combined exposure on neurotransmission, specifically dopaminergic neurotransmission, are lacking. In this study, motor coordination and dopamine content, along with the expression of tyrosine hydroxylase (TH), dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and dopamine receptors (DRs), were examined in the striatum of adult male mice following exposure to drinking water containing As, Pb, and/or Cd. We found that exposure to a metal mixture impaired motor coordination. After 4 weeks of treatment, a significant decrease in dopamine content and expression of TH, DAT, and VMAT2 was observed in the striatum of metal-mixture-treated mice, compared to the controls or single-metal-exposed groups. However, DRD1 and DRD2 expression did not significantly change with metal treatment. These results suggest that altered dopaminergic neurotransmission by the collective action of metals may contribute to metal-mixture-induced neurobehavioral disorders.
Highlights
Public Health 2021, 18, Many people around the world are exposed to toxic metals in drinking water at concentrations that exceed the allowable limits determined by the World Health Organization [1]
To assess the effects of combined exposure to As, Pb, and Cd on dopaminergic neurotransmission in the mouse brain, we evaluated the motor coordination, dopamine content, and tyrosine hydroxylase (TH), dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and dopamine receptors (DRs) expression in mice exposed to single or mixed metals
We found that combined exposure to As, Pb, and Cd downregulated the expression of DAT and VMAT2 in the striatum
Summary
Public health concerns surrounding water contamination include major toxic metal contaminants, such as arsenic (As), lead (Pb), and cadmium (Cd) [2]. Exposure to mixtures of these metals is a common and important determinant of toxicity [3]. The accumulation of these metals to toxic levels is associated with many diseases, including cancer, diabetes, respiratory disease, and cardiovascular diseases [4]. There is growing concern about the toxic effects of these metals on the central nervous system (CNS), as increasing evidence has revealed that the CNS is one of the major targets of As, Pb, and Cd [5,6]
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