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Brain Programming by Early-Life Stress

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Front. Behav. Neurosci. | doi: 10.3389/fnbeh.2018.00126

Pharmacological manipulation of DNA methylation in adult female rats normalizes behavioral consequences of early-life maltreatment

Samantha M. Keller1, Tiffany S. Doherty1 and  Tania L. Roth1*
  • 1Psychological and Brain Sciences, University of Delaware, United States

Exposure to adversity early in development alters brain and behavioral trajectories. Data continue to accumulate that epigenetic mechanisms are a mediating factor between early-life adversity and adult behavioral phenotypes. Previous work from our laboratory has shown that female Long-Evans rats exposed to maltreatment during infancy display both aberrant forced swim behavior and patterns of brain DNA methylation in adulthood. Therefore, we examined the possibility of rescuing the aberrant forced swim behavior in maltreated-adult females by administering an epigenome-modifying drug (zebularine) at a dose previously shown to normalize DNA methylation. We found that zebularine normalized behavior in the forced swim test in maltreated females, such that they performed at the levels of controls (females that had been exposed to only nurturing care during infancy). These data help link DNA methylation to an adult phenotype in our maltreatment model, and more broadly provide additional evidence that non-targeted epigenetic manipulations can change behavior associated with early-life adversity.

Keywords: epigenetics, DNMT, DNA Methylation, development, maltreatment, early-life stress, females, behavioral outcomes

Received: 18 Mar 2018; Accepted: 06 Jun 2018.

Edited by:

Richard G. Hunter, Rockefeller University, United States

Reviewed by:

Marija Kundakovic, Fordham University, United States
Roser Nadal, Autonomous University of Barcelona, Spain  

Copyright: © 2018 Keller, Doherty and Roth. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Tania L. Roth, University of Delaware, Psychological and Brain Sciences, 108 Wolf Hall, Newark, 19716, DE, United States,