Hippocampal Neurogenesis as a Critical Target of Neurotoxicants Contained in Foods

Evidence has been accumulating that environmental chemicals contained in foods can cause neurodevelopmental disabilities. However, regular developmental neurotoxicity (DNT) studies require large numbers of animals for detection of subtle dose-response changes, and it is urgent concern to establish a rapid and efficient evaluation system of DNT. Evidence from our recent studies points to the notion that adult neurogenesis in the hippocampus may represent vulnerable endpoint to cause DNT. Adult neurogenesis is the postnatal process of continued production of new neurons through the adult stage in the brain. Monitoring of granule cell lineage in the subgranular zone (SGZ) and γ-aminobutyric acid (GABA)-ergic interneurons in the dentate hilus is effective for detection of target cell populations of DNT as manifested by disruption of neurogenesis. Especially, reelin-expressing GABAergic interneurons are a useful marker to detect disruption of the migration and correct positioning of developing neurons following impairment of neurogenesis. Because axon terminal toxicants target granule cell lineage population growing dendritic processes, there may be common target mechanisms between the DNT and adult-type neurotoxicity affecting mature nervous system. Adult neurogenesis may also be a suitable endpoint for detection of DNT in a scheme of standard regular 28-day toxicity study. In other words, adult-type neurotoxicity could be detected by measuring the cellular responses in adult neurogenesis. Moreover, it should be stressed that there may be epigenome toxicity mechanisms to affect the process of hippocampal neurogenesis involving both neuronal stem cells and interneuron subpopulations, with continued disruption through the adult stage. These findings suggest that hippocampal neurogenesis is considered to be a critical target of environmental neurotoxicants contained in foods.