AUTHOR=Hashimoto Joel G. , Zhang Xiaolu , Guizzetti Marina 

TITLE=Ethanol-induced transcriptional and translational changes in Aldh1l1-Egfp/Rpl10a cortical astrocyte cultures

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 17 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2023.1193304

DOI=10.3389/fnins.2023.1193304

ISSN=1662-453X

ABSTRACT=The role astrocytes play in brain development and function has come under increased focus as the diversity of roles they are involved in has become apparent. We have previously shown ethanol exposed astrocytes alter neuronal neurite outgrowth in an in vitro co-culture system and that ethanol alters the astrocyte produced extracellular matrix (ECM) in vitro, with similar alterations in vivo. Here we utilize the translating ribosome affinity purification (TRAP) procedure in Aldh1l1-EGFP/Rpl10a transgenic mouse primary cortical astrocyte cultures to transcriptionally and translationally profile the astrocyte response to ethanol. We found a large number of differences between the total RNA pool and the translating RNA pool indicating the transcriptional state of astrocytes may not always reflect the translational state of astrocytes. In addition, we found considerable overlap between ethanol dysregulated genes in the total RNA pool and the translating RNA pool. Comparisons to published datasets indicate the in vitro model used here are most similar to PD1 or PD7 in vivo cortical astrocytes and the ethanol regulated genes showed significant overlap with models of chronic ethanol exposure in astrocytes, a model of third-trimester ethanol exposure in the hippocampus and cerebellum, and an acute model of ethanol exposure in the hippocampus. These findings will further our understanding of the effects of ethanol on astrocyte gene expression and protein translation and how these changes may alter brain development and support the use of in vitro astrocyte cultures as models of neonatal astrocytes.