Perinatal protein malnutrition results in genome-wide disruptions in hippocampal 5-hydroxymethyl cytosine at regions that can be rescued by an enriched environment

MADRID, ANDY; CHERTOFF, MARIELA; PAPALE, LIGIA; CÁNEPA EDUARDO TOMÁS; ALBERCA, CAROLINA D.; ALISCH REID

Congreso; XXXIV ANUAL MEETING SAN 2019; 2019

P15.-Perinatal protein malnutrition results in genome-wide disruptions in hippocampal 5-hydroxymethylcytosine at regions that can be rescued by an enriched environmentCarolina D. Alberca1, Ligia A. Papale3, Andy Madrid4, Reid S. Alisch3, Eduardo T. Cánepa2, Mariela Chertoff21 Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica, Laboratorio de Neuroepigenética. Buenos Aires, Argentina.,2 Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica, Laboratorio de Neuroepigenética. Buenos Aires, Argentina. CONICET- Universidad de Buenos Aires. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. (IQUIBICEN). Buenos Aires, Argentina., 3Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA., 4Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA. Neuroscience Training Program, University of Wisconsin, Madison, WI, USA.Presenting author: Carolina Desirée Alberca Doto, caro.alberca@gmail.comMaternal malnutrition remains one of the major adversities affecting newborn brain development and long-term mental health outcomes. Perinatal protein malnutrition increases the risk to develop anxiety-like behavior. Studies in mice have shown that these altered behaviors can be rescued by enriching the growth environment. The epigenetic mark 5-hydroxymethylcytosine (5hmC) is an environmentally sensitive DNA modification that is highly enriched in the brain and is associated with gene expression. Here, we examined 5hmC distribution throughout the ventral hippocampus of female mice exposed to a low protein diet (8% casein) or normal protein diet (20% casein) during gestation and lactation and that were assigned to different environmental paradigms after weaning: normal or enriched environment (i.e., social and sensory stimulation). We observed 508 differentially hydroxymethylated regions (DhMRs) associated with protein malnutrition and that an enriched environment rescued the hydroxymethylation levels at a significant number of these regions (N = 52; p-value < 0.01), including on neurologically related genes such as Nrp2, Ntm, Nav1, Sox6. Sequence motif predictions indicated that 5hmC may regulate gene expression by mediating transcription factor binding of these transcripts. Together, these findings represent a critical step toward understanding the molecular effects of the environment on the mechanisms that underlie anxiety disorders.