Mechanistic insight into neurotoxicity induced by developmental insults

Epidemiological and/or experimental studies have shown that unfavorable prenatal environmental factors, such as stress or exposure to certain neurotoxic environmental contaminants, may have adverse consequences for neurodevelopment. Alterations in neurogenesis can have harmful effects not only for the developing nervous system, but also for the adult brain where neurogenesis is believed to play a role in learning, memory, and even in depression. Many recent advances in the understanding of the complex process of nervous system development can be integrated into the field of neurotoxicology. In the past 15 years we have been using cultured neural stem or progenitor cells to investigate the effects of neurotoxic stimuli on cell survival, proliferation and differentiation, with special focus on heritable effects. This is an overview of the work performed by our group in the attempt to elucidate the mechanisms of developmental neurotoxicity and possibly provide relevant information for the understanding of the etiopathogenesis of complex brain disorders. - Highlights: • The developing nervous system is highly sensitive to toxic insults. • Neural stem cells are relevant models for mechanistic studies as well as for identifying heritable effects due to epigenetic changes. • Depending on the dose, the outcome of exposure to neurotoxicants ranges from altered proliferation and differentiation to cell death. • The elucidation of neurotoxicity mechanisms is relevant for understanding the etiopathogenesis of developmental and adult nervous system disorders.