title: Prenatal alcohol exposure causes long-term serotonin neuron deficit in mice.
abstract: BACKGROUND
  Previous work from this laboratory showed that prenatal alcohol exposure at approximately 100 mg/dl from embryonic day (E)7 to early midgestation reduced the number and retarded the migration of serotonin (5-HT) neurons in the raphe nuclei in C57BL/6 mice. In this study, we report that the deficit of 5-HT neurons found in midgestation persisted on E18 and into young adulthood.
  
  
  METHODS
  Pregnant dams were treated from E7 to E18 in three groups--(1) the alcohol group, fed with liquid diet with 25% ethanol-derived calories; (2) the isocaloric pair-fed group; and (3) the chow group for analysis of concentrations of active caspase-3--to study apoptosis at E18 in the brainstem and the number of 5-HT neurons at E18 and postnatal day 45. The concentrations of active caspase-3 were determined by using a colorimetric assay, and the 5-HT neurons were determined by immunocytochemistry.
  
  
  RESULTS
  Prenatal alcohol exposure increased the concentration of active caspase-3 in the brainstem and caused reductions in brain weight by 20% and in the total number of 5-HT-immunostaining neurons in the dorsal and median raphe nuclei by 20% at E18 as compared with those of the pair-fed and chow controls. Continuous observation from prenatal to postnatal stages showed that the reduction of 5-HT-immunostaining neurons in the dorsal and median raphe nuclei persisted in the young adult stage.
  
  
  CONCLUSIONS
  Upon prenatal alcohol exposure, an increased concentration of active caspase-3 and a decreased number of 5-HT-immunostaining neurons in the brainstem were observed at E18. The decreased number of 5-HT neurons persisted to the young adult stage of postnatal day 45. This suggests that ethanol has a long-lasting effect on 5-HT deficit. A fetal alcohol exposure-rendered lasting deficit of 5-HT and other transmitter systems may underlie the neuropsychiatric deficits in fetal alcohol spectrum disorder.
authors.affiliation: Indiana University School of Medicine, Department of Anatomy and Cell Biology, Indianapolis, Indiana 46202, USA.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Sari
authors.forename: Feng C
authors.initials: FC
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006131:Growth Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012701:Serotonin / Q000096:biosynthesis*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013995:Time
chemical_list: D006131:Growth Inhibitors; D012702:Serotonin Antagonists; D012701:Serotonin; D000431:Ethanol; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases