EXAMINATION OF DEVELOPMENTAL NEUROTOXICITY BY THE USE OF TISSUE CULTURE MODEL SYSTEMS |
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Authors: | Alfred Heller Lisa Won Barbara Heller Philip C. Hoffmann |
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Affiliation: | The University of Chicago, Department of Pharmacological and Physiological Sciences;* Illinois Institute of Technology, Department of Mathematics, Chicago, Illinois, USA |
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Abstract: | 1. The rotation-mediated three-dimensional reaggregate culture system is uniquely suited for studies on developmental neurotoxicity. In this system, it is possible to reconstruct central neuronal pathways and follow their development. 2. Exposure to drugs of abuse including methamphetamine and methylenedioxyamphetamine or the appetite suppressant, fenfluramine, reduces monoamines in the cultures in a dose-dependent manner and interrupts normal monoaminergic development. 3. While the monoaminergic neurones may attain normal rates of development following drug removal, the affected neurones are not capable of overcoming the drug-induced insults and a deficiency in monoamines persists throughout development. 4. In addition, the production of immortalized monoclonal hybrid cells obtained by fusion of fetal mesencephalic neurones with a neuroblastoma has yielded cell lines expressing a dopaminergic phenotype. 5. Such cells have been useful in establishing the relationship of neurotoxicity to cell lineage and can serve as models for the study of the cellular and molecular mechanisms of neurotoxicity. |
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Keywords: | cell lineage, dopamine, fenfluramine, immortalized hybrid cell lines, methamphetamine, methylenedioxyamphetamine, reaggregate tissue culture, serotonin. |
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