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Prenatal Alcohol Exposure Causes Long‐Term Serotonin Neuron Deficit in Mice
Author(s) -
Sari Youssef,
Zhou Feng C.
Publication year - 2004
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1097/01.alc.0000128228.08472.39
Subject(s) - immunostaining , dorsal raphe nucleus , endocrinology , raphe , immunocytochemistry , brainstem , medicine , serotonin , neuron , biology , raphe nuclei , serotonergic , neuroscience , immunohistochemistry , receptor
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.