Prenatal alcohol exposure causes long-term serotonin neuron deficit in mice

Alcohol Clin Exp Res. 2004 Jun;28(6):941-8. doi: 10.1097/01.alc.0000128228.08472.39.


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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain Stem / drug effects
  • Brain Stem / enzymology
  • Brain Stem / pathology
  • Caspase 3
  • Caspases / metabolism
  • Cell Count
  • Cell Movement / drug effects
  • Ethanol / pharmacology*
  • Female
  • Growth Inhibitors / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / drug effects*
  • Neurons / enzymology
  • Neurons / metabolism
  • Neurons / pathology*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Serotonin / biosynthesis*
  • Serotonin Antagonists / pharmacology*
  • Time


  • Growth Inhibitors
  • Serotonin Antagonists
  • Serotonin
  • Ethanol
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases