Primates exposed to cocaine in utero display reduced density and number of cerebral cortical neurons.
This study examined the effects of cocaine use during the second trimester of pregnancy on cerebral neocortical volume and density, and total number of neocortical neurons and glia in offspring. We also evaluated the extent of postnatal recovery of cytoarchitectural abnormalities previously observed in the neocortex of two-month-old primates born from cocaine-treated mothers (Lidow [1995] Synapse 21:332-334). Pregnant monkeys received cocaine orally (20 mg/kg/day) from the 40th to 102nd days of pregnancy (embryonic day [E]40-E102). On E64 and E65, the animals were injected with [(3)H]thymidine. Cerebral hemispheres of the offspring were examined at three years of age. We found a reduction in the neocortical volume and density and total number of neocortical neurons. The observed reduction in neuronal number within the neocortex was not accounted for by the increase in the number of neurons in the white matter of cocaine-exposed animals, because the number of these "extra" neurons was equal to only half that of missing neurons. We detected no significant changes in the number of neocortical glia. The cytoarchitectural abnormalities in the neocortex of prenatally cocaine-exposed three-year-old monkeys closely resembled previously described neocortical abnormalities in similarly exposed two-month-old animals: the neocortex lacked a discernible lamination; the majority of the cells labeled by [(3)H]thymidine injected during neocortical neurogenesis did not reach their proper position within the cortical plate. Therefore, postnatal maturation is not associated with significant improvement in neocortical organization in primates prenatally exposed to cocaine. There was, however, a postnatal recovery of low glial fibrillary acidic protein (GFAP) immunoreactivity previously observed in 2-month-old cocaine-exposed animals.
Lidow
M S
MS
Department of Oral and Craniofacial Biological Sciences and Program of Neuroscience, University of Maryland, Baltimore, Maryland 21201, USA. mlidow@umaryland.edu
Song
Z M
ZM
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D002452:Cell Count; D002540:Cerebral Cortex / Q000002:abnormalities / Q000187:drug effects* / Q000473:pathology; D003042:Cocaine / Q000633:toxicity*; D019970:Cocaine-Related Disorders / Q000150:complications / Q000503:physiopathology; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000002:abnormalities / Q000187:drug effects* / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008253:Macaca mulatta; D009421:Nervous System Malformations / Q000139:chemically induced* / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011379:Prognosis; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D018765:Dopamine Uptake Inhibitors; D005904:Glial Fibrillary Acidic Protein; D003042:Cocaine