Alcohol, clinical & experimental research · 2024
Alcohol and fear conditioning produce strain-specific changes in the dorsal hippocampal transcriptome of adolescent C57BL/6J and DBA/2J mice.
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Seemiller Laurel R, Goldberg Lisa R, Sebastian Aswathy, Siegel Sue Rutherford, Praul Craig, Zeid Dana, Albert Istvan, Beierle Jacob, Bryant Camron D, Gould Thomas J
Аннотация
BACKGROUND: Adolescent sensitivity to alcohol is influenced by genetic background. Data from our laboratory suggested that adolescent C57BL/6J and DBA/2J inbred mice differed in susceptibility to alcohol-induced deficits in dorsal hippocampus-dependent contextual fear learning.
METHODS: To investigate the biological underpinnings of this strain difference, we examined dorsal hippocampus gene expression using RNA-sequencing after alcohol or saline administration followed by Pavlovian fear conditioning across male and female C57BL/6J and DBA/2J adolescents.
RESULTS: Strains exhibited dramatic differences in dorsal hippocampus gene expression. Specifically, C57BL/6J and DBA/2J strains differed by 3526 transcripts in males and 2675 transcripts in females. We identified pathways likely to be involved in mediating alcohol's effects on learning, including networks associated with Chrna7, a gene encoding the nicotinic cholinergic receptor alpha 7 subunit, and Fmr1, a gene encoding the fragile X messenger ribonucleoprotein.
CONCLUSIONS: These findings provide insight into the mechanisms underlying strain differences in alcohol's effects on learning and suggest that different biological networks are recruited for learning based on genetics, sex, and alcohol exposure.
METHODS: To investigate the biological underpinnings of this strain difference, we examined dorsal hippocampus gene expression using RNA-sequencing after alcohol or saline administration followed by Pavlovian fear conditioning across male and female C57BL/6J and DBA/2J adolescents.
RESULTS: Strains exhibited dramatic differences in dorsal hippocampus gene expression. Specifically, C57BL/6J and DBA/2J strains differed by 3526 transcripts in males and 2675 transcripts in females. We identified pathways likely to be involved in mediating alcohol's effects on learning, including networks associated with Chrna7, a gene encoding the nicotinic cholinergic receptor alpha 7 subunit, and Fmr1, a gene encoding the fragile X messenger ribonucleoprotein.
CONCLUSIONS: These findings provide insight into the mechanisms underlying strain differences in alcohol's effects on learning and suggest that different biological networks are recruited for learning based on genetics, sex, and alcohol exposure.