Biomarkers for central nervous system toxicity

In the history of occupational neurotoxicology, histopathological method in animal studies played an important role in clarifying the causative agent. However, in studies on hexane or toluene, the histopathological studies gave limited evidences for adverse effects on the central nervous system. It is believed that the morphological structure in the central nervous system is robuster to chemical exposure than biochemical or physiological parameters probably because of the high plasticity of the central nervous system. Therefore, the development of molecular biomarkers for the central nervous system toxicity is needed for evaluation of the effects on the central nervous system in animals and humans. In the initial attempt of studies on biomarkers, neuro-specific or glia-specific protein was noticed as candidates for biomarkers[1]. The rat studies showed change in beta-S100, a glial marker induced by exposure to toluene in the cerebellum, which is known to be affected in toluene sniffers. However, it was unknown how such markers were involved in the toxicological process induced by exposure to toluene, so the interpretation of change in these biomarker candidates was difficult. Thus, studies on mechanism of neurotoxicity are needed to know how the candidates of biomarkers are involved in the pathological process induced by neurotoxic chemicals in the central nervous system. We recently conducted animal studies using immunohistochemistry of noradrenergic axons[2] and glial markers, as well as using proteomics approach, to understand the mechanism of 1-bromopropane neurotoxicity and to explore possible biomarkers for the central nervous system toxicity. The application of the biological methods for the development of biomarkers for the central nervous system toxicity will be discussed.