Cognitive and emotional deficits reflect altered epigenetic mechanisms in hippocampus and amygdala derived from perinatal malnutrition in a mouse model- Reversion with environmental enrichment.

CHERTOFF MARIELA

Congreso; XXXIV ANUAL MEETING SAN 2019; 2019

Argentine Society for Research in Neurosciences

Cognitive and emotional deficits reflect altered epigenetic mechanisms in hippocampus andamygdala derived from perinatal malnutrition in a mouse model- Reversion with environmentalenrichmentMariela ChertoffDepartamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and IQUIBICEN, CONICET, Argentina.The quality of the embryonic environment and postnatal experiences have a great influence on the emotional and cognitive development of the infant and the adolescent. We study the impact of perinatal protein malnutrition, using a both sexes young adult mice born from dams fed with normal protein diet (NP) or low protein diet (LP) during pregnancy and lactation. Through a preclinical PET analysis, we found evidence of changes in glucose metabolism in the hippocampus and amygdala of LP mice, suggesting a potential alteration in the function of these areas. Therefore, we performed different behavioral tests in order to evaluate emotional status and memory. We found that recognition memory was impaired and anxiety-like behavior was increased in LP mice. We observed that environmental enrichment (EE) partially reverts the emotional and cognitive deficits. In order to understand the molecular mechanisms behind this, we focus on DNA methylation pathways, finding an increased expression of DNMT3b and Gadd45b in P21 malnourished females but not in males. The5hmC seems to be an important epigenetic mechanism of brain adaptation, so, we examine the distribution of 5hmC on ventral hippocampus and we found several anxiety-related genes differentially 5hmethylated on malnourished mice, which are reverted after growing on EE. Together, these findings represent a critical step toward understanding the molecular effects of the environment on the mechanisms that underlie anxiety disorders.