Dopaminergic and serotoninergic neurotoxicity of lanthanide phosphate (TbPO₄) in developing zebrafish

Rare earth elements (REEs) are exploited for global use in manufacturing. Such activities result in their release into the environment and the transformation into more stable phosphate deposition. The objective of this study was to evaluate molecular and behavioral changes of zebrafish exposed to the synthesized terbium phosphate (TbPO₄) at concentrations of 10, 20, and 50 mg/L and to determine its potential for neurotoxicity. Metabolomics related to neurotransmitters, and assessment of transcripts and proteins were conducted to uncover the molecular mechanisms underlying TbPO₄ with emphasis on neurotransmitter systems. Exposure to 20 mg/L TbPO₄ induced larval hyperactivity and perturbed the cholinergic system in zebrafish. Based on metabolomics related to neurotransmitters, dopamine (DA), serotonin (5-HT), and many of their precursors and metabolites were decreased in abundance by TbPO₄. In addition, the expression levels of transcripts related to the synthesis, transport, receptor binding, and metabolism of DA and 5-HT were analyzed at the mRNA and protein levels. Transcript and protein levels for tyrosine hydroxylase (TH), the rate-limiting enzyme for DA synthesis, were down-regulated in larval fish. Monoamine oxidase (MAO), an enzyme that catabolizes monoamines DA and 5-HT, was also reduced in mRNA abundance. We hypothesize that DA synthesis and monoamine metabolism are associated with behavioral alterations. This study elucidates putative mechanisms and exposure risks to wildlife and humans by characterizing phosphatic REE-induced neurotoxicity in developing zebrafish.