Altered miRNA expression profile in the hypothalamus of perinatally malnourished mice.

BERARDINO BRUNO; FESSER ESTEFANIA; CHERTOFF MARIELA; CÁNEPA EDUARDO TOMÁS

Congreso; XXX REUNION ANUAL SAN; 2015

Early life stress -such as malnutrition- during the critical perinatal period modifies cellular differentiation and neurogenesis programs promoting lifetime social and cognitive disturbances. However, the role of miRNAs in the CNS linking malnutrition with behavioral deficiencies has not been described. The hypothalamus emerges as an intriguing target as it plays a crucial role in energy balance, stress response and motivated behaviors.Here, we used high-throughput sequencing to define to what extent the hypothalamic profiles of miRNA expression are perturbed in perinatally malnourished mice. CF1 dams were fed with normal protein diet (NP) or low protein diet (LP, 40%) during pregnancy and lactation, and the male offspring were analyzed at P56.We studied the predicted and validated mRNA targets of 16 differentially expressed miRNAs between NP and LP -particularly, miR-124, miR-187 and miR-204. For the prediction, a set of 9 algorithms was used: miRWalk, MicroT4, miRanda and TargetScan, among others. Due to differences in sensitivity and specificity of the algorithms, we obtained the intersection of the results in order to enhance credibility and reduce false positives. DAVID tool was used for pathway classification of predicted and validated genes. We found a significant enrichment in the axon guidance pathway, which could have potential consequences in hypothalamic functions. Moreover, several pathways related to cytoskeleton remodeling were also consistently enriched.