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

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

Congreso; Women in Bioinformatics and Data Science LA; 2020

Perinatal malnutrition programs stress responses and developmental trajectories leading to cognitive, mood and behavioral impairments later in life. Epigenetic mechanisms, such as microRNAs (miRNAs), have been proposed as the molecular basis for these effects. While miRNAs are widely studied in the literature, less attention has been paid to miRNA sequence variants, i.e. isomiRs, as potential regulators of gene expression. In this study, we aim to identify novel isomiRs that might be responsible for the phenotypic changes in anxiety-like behavior observed in malnourished rodents. For this purpose, we used our previously reported perinatal malnutrition and postweaning environmental enrichment model and analyzed the hypothalamic miRNAome through Illumina sequencing technology. Male mice were used for this experiment because an increased glucose consumption in the hypothalamus was 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 the enriched environment. We found that isomiRs are prominently expressed in the hypothalamus of young adult male mice and we described their isoform patterns. Interestingly, sequence variants within the seed region of the canonical miRNA are conserved between treatments, suggesting that such modifications might not be driven by chance. Furthermore, we identified a set of miRNAs and isomiRs that could be responsible for the phenotypic reversion of anxiety traits. The predicted mRNA targets for this set of miRNAs/isomiRs are enriched in cellular pathways that could explain behavioral differences, e.g. axon guidance and neurogenesis.IsomiRs might play an important role in epigenetic regulation in the hypothalamus of young adult male mice accounting alongside canonical miRNAs for differences seen in anxiety-like behavior of malnourished mice exposed to an enriched environment.