Exposure to enriched environment rescues anxiety-like behavior and miRNA deregulated expression induced by perinatal malnutrition while altering oligodendrocyte morphology

BRUNO G. BERARDINO; MARIELA CHERTOFF; GIANATIEMPO, OCTAVIO; CAROLINA ALBERCA; ROCÍO PRIEGUE; ANA FISZBEIN; PATRICK LONG; GABRIEL CORFAS; EDUARDO T. CÁNEPA

NEUROSCIENCE

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2019

0306-4522

Maternal malnutrition is one of the major early-lifeadversities affecting the development of newborn´s brain and isassociated with an increased risk to acquire cognitive and emotionaldeficiencies later in life. Studies in rodents have demonstrated thatexposure to an enriched environment (EE) can reverse the negativeconsequences of early adversities. However, rescue of emotional disorderscaused by perinatal malnutrition and the mechanisms involved has not beendetermined. We hypothesized that exposure to an EE may attenuate theanxiety-like disorders observed in mice subjected to perinatal proteinmalnutrition and that this could be mediated by epigenetic mechanisms.Male CF-1 mice were subject to perinatal protein malnutrition untilweaning and then exposed to an EE for 5 weeks after which small RNA-seqwas performed. In parallel, dark-light test and elevated plus maze wereconducted to evaluate anxiety traits. We found that exposure to an EEreverses the anxiety-like behavior in malnourished mice. This reversal isparalleled by the expression of three miRNAs that become dysregulated byperinatal malnutrition (miR-187-3p, miR-369-3p and miR-132-3p). The mRNAtarget prediction of these miRNAs is mostly related to axon guidancepathways. Accordingly, we also found that perinatal malnutrition leads toreduction in the cingulum size and altered oligodendrocyte morphology.These results suggest that EE-rescue of anxiety disorders derived fromperinatal malnutrition is mediated by the modulation of miRNA levelsassociated with the regulation of genes involved in axonal guidance.