Neurotoxicity mechanism of environmental chemicals and its evaluation system

Abstract

It is pivotal to assess the toxicity and safety of chemicals, including medicines, in the research field of environmental health science. Here we introduce neurotoxic mechanisms in mammals of environmental organotin and Parkinson's disease-related chemicals. We clarified that low concentrations of tributyltin decrease a-amino-3-hydroxy-5-methyl-4-isox-azolepropionic acid (AMPA)-type glutamate receptor subunit GluA2 (GluR2) expression, leading to the vulnerability of cultured neurons. That is, tributyltin reduces GluA2 prior to neuronal death. This GluA2 decrease can be used as a sensitive evaluation index of neurotoxicity, since low levels of certain chemicals, for example some agrochemicals, decrease GluA2 expression. We also elucidated the mechanisms of abnormal protein metabolism induced by low levels of two Parkinson's disease-related chemicals: 1-methyl-4-phenylpyridinium ion (MPP＋ ) and 1,2,3,4-tetrahydroiso-quinoline derivatives. It is expected that these findings will become clues in accurately evaluating the toxicity of chemicals and/or in investigating the causes of disease.