Divergent and overlapping hippocampal and cerebellar transcriptome responses following developmental ethanol exposure during the secondary neurogenic period.

ABSTRACT: Purpose: Fetal alcohol spectrum disorders (FASD) result from ethanol exposure to the developing fetus. FASD occur in up to 1-5% of live births in the United States and there currently is no cure. Ethanol exposure to the developing central nervous system (CNS) has profound effects on learning and memory, impulse control, and motor function, resulting from neuropathology. The purpose of the current study was to perform transcriptome analysis to evaluate the effects of early postnatal ethanol exposure in the hippocampus and cerebellum. Methods: Postnatal C57BL/6 mice were treated with 4g/kg of ethanol from P4-P9, brains were harvested 24h after the final treatment at P10, hippocampi and cerebella were microdissected, RNA was isolated, and RNASeq analysis was performed. We compared differences in gene expression, sex-dependent expression, and global biological pathways associated with disruptions in hippocampal and cerebellar genes between the ethanol and vehicle treated neonates. Results: Ethanol caused both an up and down regulation of genes associated with the hippocampus and cerebellum, which may result in the disruption of normal circuitry and maturation and growth in these brain regions. Ethanol increased the expression of genes associated with the S phase of the cell cycle in both the hippocampus and cerebellum. In the cerebellum, ethanol increased effector gene expression, and in the hippocampus, genes associated with different interneuron lineages were altered. Postnatal ethanol exposure also resulted in altered expression of genes associated with oligodendrocyte lineages and myelination, along with alterations in microglia associated genes. Conclusion: Collectively, these data indicate that ethanol has profound effects on the hippocampus and cerebellum, resulting in alterations of gene expression and biological pathways regulating neurodevelopment. These studies may have important implications concerning alcohol-induced neuropathology and the neurological effects seen across the life span in FASD.

ORGANISM(S): Mus musculus

PROVIDER: GSE166196 | GEO | 2021/08/04

REPOSITORIES: GEO