The effects of sodium butyrate (NaB) and maltreatment early in postnatal development on DNA methylation in the hippocampus and amygdala of adult male rats
Date
2019
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Publisher
University of Delaware
Abstract
Early life stress, especially childhood maltreatment, increases the risk for cognitive dysfunction and mental problems later in life. Studies have sought to identify how these phenotypes come about by examining structural and functional changes in various brain regions. Recent work has also focused on identifying whether changes in DNA methylation, an epigenetic modification that helps regulate gene transcription important for the structural and functional capacity of the brain, is also responsible for phenotypic outcomes. Using a rat model, we investigated whether maltreatment leaves long-term epigenetic modifications on DNA associated with the brain-derived neurotrophic factor (bdnf) gene in the adult amygdala and hippocampus and whether administering an epigenome modifying drug (sodium butyrate, NaB) at the time of maltreatment prevents these epigenetic modifications. We focused on the bdnf gene as it is critical for structural and functional capacity of the brain and known to be sensitive to early life stress. During first post-natal week, infant male rats were either administered NaB or a vehicle solution and exposed to either maltreatment or nurturing maternal care. We then assessed DNA methylation after pups reached adulthood. We replicate observations we made in a previous report that exposure to maltreatment alters bdnf DNA methylation in the amygdala and hippocampus. We also find concurrent administration of NaB with maltreatment capable of changing patterns of methylation. These results provide further empirical support that DNA methylation modifications are biological consequences of experiences within the caregiving environment and highlight the ability to potentially intervene and change epigenetic trajectories.