title: A computational model for neocortical neuronogenesis predicts ethanol-induced neocortical neuron number deficits.
abstract: We have developed a computational model that allows for the evaluation of normal and perturbed neurodevelopmental processes. This mathematical construct is used to test the hypothesis that reduced neuronal production is the critical mechanism behind fetal alcohol syndrome. Model predictions of normal neurodevelopment match independent stereological measures but challenge estimates generated using a previously published model of normal neocortical neuronogenesis. Evaluation of data showing an increased cell cycle length after prenatal exposure to ethanol during neocortical neuronogenesis yields predictions of cellular deficits that can account for the permanent neocortical neuronal loss seen in rodents exposed to ethanol concentrations of public health relevance.
authors.affiliation: Institute for Risk Analysis and Risk Communication, Department of Environmental Health, University of Washington, Seattle, Wash 98105-6099, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Gohlke
authors.forename: W C
authors.initials: WC
authors.lastname: Griffith
authors.forename: S M
authors.initials: SM
authors.lastname: Bartell
authors.forename: T A
authors.initials: TA
authors.lastname: Lewandowski
authors.forename: E M
authors.initials: EM
authors.lastname: Faustman
mesh_terms: D000818:Animals; D017209:Apoptosis; D002452:Cell Count; D002492:Central Nervous System Depressants / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology*; D006801:Humans; D008954:Models, Biological; D019579:Neocortex / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D015203:Reproducibility of Results
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol