Analyzing the effects of perinatal protein malnutrition on the miRNAome of young adult male mice

OCTAVIO GIANATIEMPO; BRUNO G. BERARDINO; ROCÍO PRIEGUE; EDUARDO T. CÁNEPA

Congreso; 1st Congress of Women in Bioinformatics and Data Science Latin America; 2020

Women in Bioinformatics and Data Science Latin America

Perinatal malnutrition programs stress responses and developmental trajectories leading to cognitive, moodand behavioral impairments later in life. Epigenetic mechanisms, such as microRNAs (miRNAs), have beenproposed as the molecular basis for these effects. While miRNAs are widely studied in the literature, lessattention has been paid to miRNA sequence variants, i.e. isomiRs, as potential regulators of geneexpression. In this study, we aim to identify novel isomiRs that might be responsible for the phenotypicchanges in anxiety-like behavior observed in malnourished rodents.For this purpose, we used our previously reported perinatal malnutrition and postweaning environmentalenrichment model and analyzed the hypothalamic miRNAome through Illumina sequencing technology.Male mice were used for this experiment because an increased glucose consumption in the hypothalamuswas shown in PET scans. This difference was absent in female animals. In this model, exposure to a low-protein diet during gestation and lactation induces anxiety-like behaviors that can be reverted by theenriched environment.We found that isomiRs are prominently expressed in the hypothalamus of young adult male mice and wedescribed their isoform patterns. Interestingly, sequence variants within the seed region of the canonicalmiRNA are conserved between treatments, suggesting that such modifications might not be driven bychance. Furthermore, we identified a set of miRNAs and isomiRs that could be responsible for thephenotypic reversion of anxiety traits. The predicted mRNA targets for this set of miRNAs/isomiRs areenriched in cellular pathways that could explain behavioral differences, e.g. axon guidance andneurogenesis.IsomiRs might play an important role in epigenetic regulation in the hypothalamus of young adult male miceaccounting alongside canonical miRNAs for differences seen in anxiety-like behavior of malnourished miceexposed to an enriched environment.