Neurobehavioral and Dopaminergic Dysfunctions Induced by Mixed Metal Exposure in C57BL/6 Mice

Abstract

Background: Aluminum (Al), lead (Pb), and mercury (Hg) are major environmental pollutants, and a large population may be simultaneously exposed to these metals. However, studies on the potential neurobehavioral effects of mixed exposure to Al, Pb, and Hg are lacking. Objectives: This study aimed to evaluate neurobehavioral changes in mice following combined exposure to Al, Pb, and Hg and to investigate the effects of this exposure on dopaminergic neurotransmission within the striatum. Methods: In this study, C57BL/6 mice (n = 10 per group) were assigned to control and metal-treated groups. Changes in motor coordination and locomotor activity that occurred when mice were simultaneously exposed to these metals via drinking water for 28 days were measured using the rotarod and open field tests. In addition, dopamine content and key factors involved in dopaminergic neurotransmission in the striatum were evaluated using real-time PCR and Western blot analysis. Results: The mixed metal exposure decreased motor function and significantly reduced the content of dopamine in the striatum of the experimental mice (P < 0.001). Expression of tyrosine hydroxylase, vesicular monoamine transporter 2, and dopamine receptor D1, which are involved in dopaminergic neurotransmission in the striatum, was significantly decreased (P < 0.01), whereas expression of the dopamine transporter was significantly increased (P < 0.05). Dopamine receptor D2 expression was not significantly changed by the mixed metal exposure. Conclusions: These results suggest that mixed exposure to Al, Pb, and Hg inhibits normal dopaminergic neurotransmission, resulting in neurobehavioral disorders.