Use of aggregating brain cell cultures to study developmental effects of organophosphorus insecticides

Aggregating brain cell cultures of fetal rat telencephalon can be grown in a chemically defined medium for extended periods of time. After a phase of intense mitotic activity, these three-dimensional cell cultures undergo ext ensive morphological differentiation, including synaptogenesis and myelinat ion. To study the developmental toxicity of organophosphorus compounds (OP) , aggregating brain cell cultures were treated with parathion. Protein cont ent and cell type-specific enzyme activities were not affected up to a conc entration of 10(-5) M. Gliosis, characterized by an increased staining for glial fibrillary acidic protein (GFAP), was observed in immature and in dif ferentiated cells. In contrast, uridine incorporation and myelin basic prot ein (MBP) immunoreactivity revealed strong differences in sensitivity betwe en these two developmental stages. These results are in agreement with the view that in vivo the development-dependent toxicity is not only due to cha nges in hepatic detoxification, but also to age-related modifications in th e susceptibility of the different populations of brain cells. Furthermore, they underline the usefulness of histotypic culture systems with a high dev elopmental potential, such as aggregating brain cell cultures, and stress t he importance of applying a large range of criteria for testing the develop mental toxicity of potential neurotoxicants. (C) 2000 Inter Press, Inc.