Use of human central nervous system cell cultures in neurotoxicity testing

The nervous system is highly sensitive to toxic damage. Many environmental contaminants can produce acute or chronic neurological effects, and contrib ute to neural damage and cell death in neurodegenerative diseases. The util ization of primary cultures of neurons and glial cells is an essential step investigating the specificity of the effects and mechanisms of action of t he test chemical. If we take into account interspecies differences, culture s of human central nervous system (CNS) cells would be the best-suited test models for in vitro neurotoxicity testing. For practical and ethical reaso ns, human neuronal and glial cultures cannot be used for routine neurotoxic ity testing, but they may be very useful for validating results from murine cultures and to address specific toxicity questions. For instance, we are investigating the action of agents producing oxygen radical damage in CNS c ells. Oxidative stress is known to trigger apoptotic death of neurons and l ead to neurodegeneration. A useful model in which to study these processes could be neuronal cultures obtained from CNS tissue with trisomy. 21. since these cells suffer oxidative stress and apoptotic cell death in vitro. Bes ides primary cultures, human-derived clonal cell lines such as neuroblastom a SH-SY5Y can offer a first-step approach in neurotoxicity testing. (C) 199 9 Elsevier Science Ltd. All rights reserved.