Selective direct toxicity of cocaine on fetal mouse neurons. Teratogenic implications of neurite and apoptotic neuronal loss.
This chapter reviews epidemiologic clinical surveys and experimental animal studies, indicating that cocaine may induce severe teratogenic effects on the developing brain. Evidence for direct toxic effects is next presented. Using cocultures of embryonic brain cells, we demonstrate that cocaine selectively affects neuronal cells, first causing a dramatic reduction in the number and length of neurites, then extensive neuronal death by apoptosis. By contrast, cocaine affected neither the abundance of astroglial cells nor their glial fibrillary acidic protein content. These effects are not due to cocaine metabolites. The contributions of indirect and direct effects that could account for cocaine neuroteratogenicity are finally discussed.
Cell Biology Unit, Christian de Duve Institute of Cellular Pathology, Brussels, Belgium. Nassogne@cell.ucl.ac.be
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Nassogne
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Evrard
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Courtoy
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000002:abnormalities / Q000187:drug effects* / Q000473:pathology; D003042:Cocaine / Q000633:toxicity*; D005260:Female; D005317:Fetal Growth Retardation; D005333:Fetus; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D051379:Mice; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D019966:Substance-Related Disorders; D013723:Teratogens
D013723:Teratogens; D003042:Cocaine