CHANGES IN EPIGENETIC REGULATION IN THE PERIAQUEDUCTAL GREY DUE TO EARLY LIFE ADVERSITY
Date
2024-05
Authors
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Publisher
University of Delaware
Abstract
Maternal buffering, or the availability of a caregiver during an aversive event, has
the capacity to change brain connectivity and alter the trajectory of behavioral and
psychopathological outcomes. The underlying molecular mechanisms for this are poorly
understood. Epigenetics, literally translating to “above the genome”, is one plausible body of
mechanisms, as epigenetic regulation of gene expression via DNA methylation is highly
attuned to early life experiences and serves as a marker of psychopathology in the brain.
To explore this, in this study we exposed rat pups to a predator odor (to simulate
aversity) with or without their mom present (to manipulate maternal buffering). We then
measured DNA methylation and expression of the gene for Brain Derived Neurotrophic Factor
(BDNF) in the Periaqueductal Gray (PAG). Expression and methylation of Bdnf DNA is
profoundly affected by early life experiences, and the PAG is a brain region shown to be
involved in fear circuitry. We know from prior work that repeated exposure to a predator odor
during development has the capacity to reduce fear responsiveness to that same odor later in
life. Further, there is a dearth of literature looking at epigenetic changes in the PAG that might
be associated with aversive early life experiences.
First, our data demonstrate the susceptibility of the PAG to epigenetic changes as a
result of early life experiences. Second, our data highlight the importance of having multiple
time points in a study, as we found that patterns of gene expression and methylation varied at
the two collection points. Finally, our data suggest that DNA methylation may be at least
partially responsible for the changes in gene expression driven by predator odor and maternal
presence.