Developmental cadmium exposure disrupts zebrafish vestibular calcium channels interfering with otolith formation and inner ear function

• Published in: Neurotoxicology (Park Forest South) Vol. 96; pp. 129 - 139
• Main Authors: Green, Adrian J., Wall, Alex R., Weeks, Ryan D., Mattingly, Carolyn J., Marsden, Kurt C., Planchart, Antonio
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2023
• Subjects: Animals; Behavior; Cadmium; Cadmium - toxicity; Developmental toxicology; Otolithic Membrane; P2X receptor; Vestibular Diseases; Vestibular system; Vestibule, Labyrinth; Zebrafish; Cadmium; Zebrafish; Developmental toxicology; Behavior; Vestibular system; P2X receptor
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2023.04.006

Dizziness or balance problems are estimated to affect approximately 3.3 million children aged three to 17 years. These disorders develop from a breakdown in the balance control system and can be caused by anything that affects the inner ear or the brain, including exposure to environmental toxicants. One potential environmental toxicant linked to balance disorders is cadmium, an extremely toxic metal that occurs naturally in the earth’s crust and is released as a byproduct of industrial processes. Cadmium is associated with balance and vestibular dysfunction in adults exposed occupationally, but little is known about the developmental effects of low-concentration cadmium exposure. Our findings indicate that zebrafish exposed to 10–60 parts per billion (ppb) cadmium from four hours post-fertilization (hpf) to seven days post-fertilization (dpf) exhibit abnormal behaviors, including pronounced increases in auditory sensitivity and circling behavior, both of which are linked to reductions in otolith growth and are rescued by the addition of calcium to the media. Pharmacological intervention shows that agonist-induced activation of the P2X calcium ion channel in the presence of cadmium restores otolith size. In conclusion, cadmium-induced ototoxicity is linked to vestibular-based behavioral abnormalities and auditory sensitivity following developmental exposure, and calcium ion channel function is associated with these defects. [Display omitted] •Low-concentration developmental cadmium exposure induces hyperactivity and circling in larval zebrafish.•Cadmium exposure decreases otolith size and increases startle sensitivity through inner ear calcium ion channel disruption.•Changes in startle sensitivity are independent of neuromast cells.•Pharmacological intervention demonstrates that calcium ion channels P2X and TRPV6 are crucial to the observed phenotypes.