Use of Human Central Nervous System Cell Cultures in Neurotoxicity Testing.

Abstract

The nervous system is highly sensitive to toxic damage. Many environmental contaminants can produce acute or chronic neurological effects, and contribute to neural damage and cell death in neurodegenerative diseases. The utilization of primary cultures of neurons and glial cells is an essential step in investigating the specificity of the effects and mechanisms of action of the test chemical. If we take into account interspecies differences, cultures of human central nervous system (CNS) cells would be the best-suited test models for in vitro neurotoxicity testing. For practical and ethical reasons, human neuronal and glial cultures cannot be used for routine neurotoxicity 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 cells. Oxidative stress is known to trigger apoptotic death of neurons and lead 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. Besides primary cultures, human-derived clonal cell lines such as neuroblastoma SH-SY5Y can offer a first-step approach in neurotoxicity testing.