Changes in gene expression on the ventral hippocampus in a mice model of perinatal protein malnutrition and its rescue by enriched environment: Relation with the epigenetic mark 5-hydroxymethylcytosine (5hmC)

ALBERCA, CAROLINA D.; PAPALE, LIGIA; MADRID, ANDY; ALISCH REID; CANEPA, EDUARDO T; CHERTOFF, MARIELA

Congreso; XXXVI Reunion anual de la sociedad argentina de investigación en neurociencias; 2021

sociedad argentina de investigación en neurociencias

Perinatal protein malnutrition increases the risk to develop anxiety and depression. Studies in mice have shown that these altered behaviors can be rescued by and enriched environment (EE). The epigenetic mark 5-hydroxymethylcytosine (5hmC) is an environmentally sensitive DNA modification that is highly enriched in the brain and its association with gene expression is understudied. We previously analyzed the distribution of 5hmC on the ventral hippocampus in a mouse model of perinatal protein malnutrition (40% of the required amount of protein) and subsequent exposition to an EE after weaning. We observed that malnutrition is associated with low levels of this epigenetic mark 5hmC in genes related to the development of the CNS. Moreover, the exposure to an EE under the perinatal malnutrition model increases the level of this mark in genes related to those terms. In this work, we analyzed the genome-wide expression profile by RNAseq. A significant number of genes affected by malnutrition reverted their expression levels due to the EE. The changes in gene expression are observed mainly on neurons and astrocytes. Although the 5hmC mark does not appear to be associated with the transcription process under the malnutrition model, it may be regulating the transcriptional levels of genes affected by the EE. Together, these findings represent a critical step toward understanding the molecular effects of the environment on the mechanisms that underlie anxiety disorders.