Identification and characterization of novel hypothalamic isomiRs related to anxiety-like behavior induced by perinatal protein malnutrition

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

Congreso; XXXV Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2020

Sociedad Argentina de Investigación en Neurociencias

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. In this study, we aim to identify and characterize novel isomiRs that might be responsible for the anxiety-like behavior observed in malnourished rodents and which is reverted by an enriched environment. For this purpose, we analyzed the hypothalamic miRNAome through Illumina sequencing technology. Hypothalamus was chosen based on previous PET results. We found that isomiRs are prominently expressed in the hypothalamus of young adult male mice and we described their isoform patterns. 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 are in accordance with RNA-seq results for malnourished and control mice. These targets were 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.