Abstract
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.
Highlights
The period after birth is a sensitive period during which environmental experiences are capable of altering the trajectory of brain development (Greenough et al, 1987; Rice and Barone, 2000; Knudsen, 2004)
Previous work from our lab has shown that female rodents exposed to brief bouts of daily caregiver maltreatment exhibit as adults mild deficits in novel object recognition (NOR) and an increased latency to become immobile in the forced swim test (Doherty et al, 2017)
This suggests that animals with maltreatment history display altered behavior in the forced swim test and zebularine administration in adulthood was able to normalize this behavior measure
Summary
The period after birth is a sensitive period during which environmental experiences are capable of altering the trajectory of brain development (Greenough et al, 1987; Rice and Barone, 2000; Knudsen, 2004). Our laboratory implements a rodent model of caregiver maltreatment (Blaze and Roth, 2013, 2017; Blaze et al, 2013, 2015; Doherty et al, 2016, 2017) to better understand the Maltreatment, Methylation and Forced Swim Behavior consequences of early adversity on brain and behavioral development. Previous work from our lab has shown that female rodents exposed to brief bouts of daily caregiver maltreatment exhibit as adults mild deficits in novel object recognition (NOR) and an increased latency to become immobile in the forced swim test (Doherty et al, 2017). When animals were tested on these behavioral assays in adolescence, no differences were observed in behavioral performance between animals with a history of maltreatment relative to animals with a history of nurturing care in infancy (Doherty et al, 2017)
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