Early Ethanol Exposure Inhibits the Differentiation of Hippocampal Dentate Gyrus Granule Cells in a Mouse Model of Fetal Alcohol Spectrum Disorders

Wenhua Xu, Hui Li, Caigu He, Jacqueline Frank, Gang Chen

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background: Alcohol consumption during pregnancy may damage the developing central nervous system of the fetus and lead to brain structural and functional deficits in the children, known as fetal alcohol spectrum disorders. The underlying mechanisms have not been fully elucidated. Previously, using a third trimester–equivalent mouse model, ethanol (EtOH)-induced behavioral deficits (including spatial learning and memory dysfunction) in the mice were detected on postnatal day (PD) 35. The hippocampal formation is critically involved in spatial learning/memory and contains 2 major neuron populations: the pyramidal cells in the hippocampus proper and the dentate gyrus granule cells (DGGCs) in the dentate gyrus (DG). In rodents, while the pyramidal cells are almost exclusively generated prenatally, the DG granule neurons are majorly generated during the first 2 weeks postnatally, which coincides with the period of EtOH exposure in our mouse model. Therefore, in the current study the effects of EtOH exposure on the development of the DGGCs were examined. Methods: C57BL/6 mice were treated with 4 g/kg of EtOH by intubation on PD 4 to 10 to mimic alcohol exposure to the fetus during the third trimester in humans, and the development of DGGCs was examined by immunohistochemistry and quantified on PD 35. Results: EtOH exposure does not affect the number of total or newly generated DGGCs, but reduces the number of mature DGGCs on PD 35 in both male and female mice. The ratio of immature DGGCs over total DGGCs was increased, and the ratio of mature DGGCs over total DGGCs was decreased by EtOH exposure. In addition, no sex-dependent effects of EtOH treatment were detected. Conclusion: Our data indicate that EtOH exposure in mice during PD 4 to 10 does not affect the generation/proliferation but inhibits the differentiation of the DGGCs on PD 35.

Original languageEnglish
Pages (from-to)1112-1122
Number of pages11
JournalAlcoholism: Clinical and Experimental Research
Issue number5
StatePublished - May 1 2020

Bibliographical note

Funding Information:
We thank Dr. Wendy Katz for histology service and Ms. Liying Wu for experimental assistance in the study. We would also like to thank the UK Light Microscopy Core Facility, which is supported by the Vice President for Research, for microscopy support. Special thanks to Dr. Thomas Wilkop for very valuable assistance in microscopy imaging.

Publisher Copyright:
© 2020 by the Research Society on Alcoholism


  • Alcohol
  • Dentate Gyrus
  • Fetal Alcohol Spectrum Disorders
  • Granule Cell Differentiation
  • Hippocampus

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health


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