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

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.