Cadmium Disrupts Vestibular Function by Interfering with Otolith Formation
Abstract Cadmium (Cd 2+ ) is a transition metal found ubiquitously in the earth’s crust and is extracted in the production of other metals such as copper, lead, and zinc 1,2 . Human exposure to Cd 2+ occurs through food consumption, cigarette smoking, and the combustion of fossil fuels. Cd 2+ has been shown to be nephrotoxic, neurotoxic, and osteotoxic, and is a known carcinogen. Animal studies and epidemiological studies have linked prenatal Cd 2+ exposure to hyperactivity and balance disorders although the mechanisms remain unknown. In this study we show that zebrafish developmentally exposed to Cd 2+ exhibit abnormal otolith development and show an increased tendency to swim in circles, observations that are consistent with an otolith-mediated vestibular defect, in addition to being hyperactive. We also demonstrate that the addition of calcium rescues otolith malformation and reduces circling behavior but has no ameliorating effect on hyperactivity, suggesting that hyperactivity and balance disorders in human populations exposed to Cd are manifestations of separate underlying molecular pathways.