Neurotoxicity and brain metabolic dysfunction induced by long-term food-derived arsenic exposure

Rice consumption are a major cause of long-term exposure to arsenic. However, the exact mechanism of the neurotoxic action caused by arsenic exposure remain elusive. The purpose of this study was to investigate the effects of arsenic exposure on the behavior and neuronal structure of Caenorhabditis elegans, followed by the establishment of a 14-month mice model to simulate long-term effects. To elucidate the toxic effects of arsenic on brain metabolism, comprehensive analyses of neurotransmitter content and brain metabolomics were conducted. The findings demonstrated that arsenic exposure led to behavioral impairment, reduced levels of glutamatergic, GABAergic, dopaminergic and serotonergic neurotransmitters, as well as structural abnormalities. The majority of amino acid and fatty acid compounds were found to be upregulated in the hippocampus and cortical tissues. Respectively, an increase in nucleic acid and hydroxy acid-related compounds was observed in hippocampal tissues, while an upregulation of purine ribose-related compounds was detected in cortical tissues. The identified differential metabolites were primarily impacted by glutathione metabolism, arginine and proline metabolism, as well as alanine, aspartate, and glutamate metabolism. Correlation analysis of the hippocampus and cortex yielded compelling evidence of a strong association between glutamate and the majority of the presented metabolites.