Developmental administration of valproic acid alters DNA methylation and maternal behavior
Exposure to adversity in early development has powerful and potentially lasting consequences on behavior. Previous work in our laboratory using female Long-Evans rats has demonstrated that exposure to early-life maltreatment manifests into alterations in dam behavior, including a perpetuation of the maltreatment phenotype. These observed behavioral changes coincide with changes in epigenetic activity in the prefrontal cortex (PFC). Further, treating dams with a chromatin modifying agent (Zebularine) normalizes methylation and maltreatment phenotypes, suggesting a link between epigenetic programming and phenotypic outcomes. Here, we sought to investigate if administration of a chromatin modifying agent concurrent with the experience of maltreatment normalizes epigenetic activity associated with maltreatment and alters behavioral trajectories. Administration of valproic acid (VPA) transiently lowered levels of global DNA methylation in the PFC, regardless of exposure to nurturing care or maltreatment. When VPA-exposed animals reached adulthood, they engaged in more adverse behaviors toward their offspring. These data provide further evidence linking epigenetic changes in the developing brain with effects on behavior.
This is the peer reviewed version of the following article: Collins, N. J., Zimmerman, C. W., Phillips, N. L. H., Fern, S., Doherty, T. S., & Roth, T. L. (2022). Developmental administration of valproic acid alters DNA methylation and maternal behavior. Developmental Psychobiology, 64, 1– 14. https://doi.org/10.1002/dev.22231, which has been published in final form at https://doi.org/10.1002/dev.22231. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. This article will be embargoed until 03/14/2023.
early-life adversity, maltreatment, prefrontal cortex, valproic acid
Collins, N. J., Zimmerman, C. W., Phillips, N. L. H., Fern, S., Doherty, T. S., & Roth, T. L. (2022). Developmental administration of valproic acid alters DNA methylation and maternal behavior. Developmental Psychobiology, 64, 1– 14. https://doi.org/10.1002/dev.22231