Perinatal protein malnutrition results in genome-wide disruptions 5-hydroxymethylcytosine at regions that can be restored to control levels by an enriched environment.

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

EPIGENETICS

LANDES BIOSCIENCE

Lugar: Austin, Texas; Año: 2020

1559-2294

AbstractMaternal malnutrition remains one of the major adversities affecting brain development and long-term mental health outcomes, increasing the risk to develop anxiety and depressive disorders. We have previously shown that malnutrition-induced anxiety-like behaviors that can be rescued by a social and sensory enriched environment in male mice. Here, we expand these findings to adult female mice and profile genome-wide ventral hippocampal 5hmC levels related to malnutrition-induced anxiety-like behaviors and their rescue by sensory enriched environment. This approach revealed 508 differentially hydroxymethylated genes associated with protein malnutrition and that a significant number of these genes (N = 34) exhibited a restored 5hmC profile to control levels following exposure to an enriched environment, including genes involved in neuronal functions like dendrite outgrowth, axon guidance, and maintenance of neuronal circuits (e.g., Fltr3, Itsn1, Lman1, Lsamp, Nav, and Ror1) and epigenetic mechanisms (e.g., Hdac9 and Dicer1). Sequence motif predictions indicated that 5hmC may be modulating the binding of transcription factors for several of these transcripts, suggesting a regulatory role for 5hmC in response to perinatal malnutrition and exposure to an enriched environment. Together, these findings establish a role for 5hmC in early-life malnutrition and reveal genes linked to malnutrition-induced anxious behaviors that are mitigated by a social and sensory enriched environment.Keywords: 5-hydroxymethylcytosine, Perinatal Malnutrition, Enriched Environment, Anxiety, Ventral Hippocampus, Epigenetics, Neuronal Development.