Role of microRNAs in the establishment of cognitive and emotive deficits derived from perinatal protein malnutrition

BERARDINO BG

Congreso; XXXI Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); 2017

Early life stress -such as maternal malnutrition- during the critical perinatal period modifies cellular differentiation and neurogenesis programs promoting lifetime social and cognitive disturbances. However, the role of microRNAs in the CNS linking malnutrition with behavioral deficiencies has not been described.First, we found that miRNA biogenesis pathway was affected in low-protein maternally malnourished mice (LP) compared to their normal-protein fed counterparts (NP). Additionally, we found an increase in anxiety-like behavior and impaired memory. Both emotional and cognitive phenotypes in LP mice could be reversed by an enriched environment post weaning. A global high-throughput sequencing analysis of miRNAs in the hypothalamus suggested three miRNAs (miR-187-3p, miR-132-3p and miR-369-3p) that could be part of the molecular basis of the behavioral phenotype. The expression of miR-132-3p was shown to be negatively correlated with BDNF expression. Axon guidance pathway was enriched among the pathways to be potentially regulated by the target mRNAs predicted to interact with the altered miRNAs. Consistently, perinatal malnutrition and EE affected myelination and oligodendrocyte morphology.Alterations in the emotional and cognitive behavior of LP mice could have molecular bases in the deregulation of miRNAs that affect axonal targeting, potentially through BDNF. On the other hand, the phenotypic reversal may be due, in part, to the increased efficiency of myelination in face of environmental enrichment. These results suggest that miRNAs could play a role in neuroplasticity, allowing adaptive responses to adverse environments.