Project description:Adolescent sensitivity to alcohol is predictive of later alcohol use and is influenced by genetic background. Data from our laboratory suggested that adolescent C57BL/6J and DBA/2J inbred mice differed in susceptibility to dorsal hippocampus-dependent contextual fear learning deficits after acute alcohol exposure. To investigate the biological underpinnings of this strain difference, we examined dorsal hippocampus gene expression via RNA-sequencing after alcohol and/or fear conditioning across male and female C57BL/6J and DBA/2J adolescents. Strains exhibited dramatic differences in dorsal hippocampal gene expression. Specifically, C57BL/6J and DBA/2J strains differed in 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 and Fmr1. 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.
Project description:BACKGROUND: Human SP-A1 and SP-A2, encoded by SFTPA1 and SFTPA2 and their genetic variants differentially impact alveolar macrophage (AM) functions and regulation, including the miRNome. We investigated whether miRNome differences previously observed between AM from SP-A2 and SP-A1/SP-A2 mice are due to continued qualitative differences or a delayed response of mice carrying a single gene. METHODS: Human transgenic (hTG) mice, carrying SP-A2 or both SP-A genes and SP-A-KO mice were exposed to filtered air (FA) or O3. AM miRNA levels, target gene expression and pathways determined 18 h after O3 exposure. RESULTS: We found: (a) Differences in miRNome due to sex, SP-A genotype, and exposure; (b) miRNome of both sexes was largely downregulated by O3 ; co-ex had fewer changed (≥2X) miRNAs than either group. (c) the number and direction of expression of genes with significant changes in males and females in co-ex is almost the opposite of those in SP-A2; (iv) The same pathways were found in the studied groups; (e) O3 exposure attenuated sex differences; a higher number of genotype-dependent and genotype-independent miRNAs was common in both sexes after O3 exposure. CONCLUSION: Qualitative differences between SP-A2 and co-ex persist 18 h post-O3, and O3 attenuates sex differences.
