ALTERED EPIGENETIC MECHANISMS AND BEHAVIORAL DEFICITS DERIVED FROM PERINATAL MALNUTRITION: LESSONS FROM A MOUSE MODEL.

CHERTOFF, MARIELA; ALBERCA, CAROLINA D.; FESSER, ESTEFANÍA A.; BERARDINO, BRUNO G.; CÁNEPA EDUARDO TOMÁS

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

Perinatal period is a critical stage for individual development.The quality of the embryonic environment andpostnatal experiences have a great influence on theemotional and cognitive development of the infant andthe adolescent. Early life adversities can modulate theexpression of molecules involved in neuronal plasticitycontributing to alter developing neuronal circuits trajectories.We study the impact of perinatal protein malnutrition,using a both sexes mice born from dams fed withnormal protein diet (NP-20% of protein) or low proteindiet (LP-8% of protein) during pregnancy and lactation.Interestingly, malnourished dams provide a lesser andmore fragmented maternal care than their normally fedcounterparts. This altered behavior was associated withan increased anxiety-like behavior and a reduction onglucocorticoid receptor in the hippocampus. In the pups,through a preclinical PET analysis, we found evidenceof changes in glucose metabolism in the hippocampusand prefrontal cortex of LP mice, suggesting a potentialalteration in the function of these areas. Therefore, weperformed in F1 mice different behavioral tests in orderto evaluate emotional status, social cognition and memory.We analyzed the performance of NP and LP animalsin learning and memory tests that aim to evaluate thesocial cognition. As a result, we found that contextualrecognition memory, social interaction and social memorywere impaired in LP mice. In addition, anxiety-likebehavior was increased in LP mice. In order to understandthe molecular mechanisms behind this, we focuson DNA methylation and stress pathways, finding anincreased expression of DNMT3b and Gadd45b in P21malnourished females but not in males. We also observeda deregulation of the expression in genes linkedto the glutamatergic and gabaergic pathways in the upstreammaintenance of the E / I balance in adults LPmice. We observed that environmental enrichment (EE)partially reverts the emotional and cognitive deficits. The5hmC seems to be an important epigenetic mechanismsof brain adaptation, so, we examine the distribution of5hmC on ventral hippocampus and we found severalanxiety-related genes differentially 5hmethylated on malnourishedmice, which are reverted after growing on EE.Together, these findings represent a critical step towardunderstanding the molecular effects of the environmenton the mechanisms that underlie behavioral disorderscaused by perinatal protein malnutrition.