Changes in Epigenetic Regulation in the Periaqueductal Gray Due to Predator Odorant Exposure and Maternal Separation

• Miguel Prysakar, Neuroscience, University of Delaware

• Tania Roth, Psychological and Brain Sciences, University of Delaware

Maternal buffering, or the availability of a caregiver during an aversive event, hasthe capacity to alter the trajectory of psychopathological outcomes, change brain connectivity, and decrease fear responsiveness. However, if this behavioral change is being driven by maternal behavioral changes, or associated changes in the brain of the offspring, is poorly understood. 

Epigenetics, literally translating to “above the genome”, is one mechanism at the cellular level associated with changes in our early life experiences, and has been proposed to be a marker of psychopathology in the brain. This study looks at the methylation and expression of the gene for  Brain Derived Neurotrophic Factor (BDNF) in the Periaqueductal Gray (PAG). Epigenetic changes in other brain regions, such as decreased BDNF methylation, have been associated with the development of many mental illnesses, including depression, as BDNF is an important neurotrophin for learning and memory, neuronal plasticity, and modulates neurotransmission. 

The Periaqueductal Gray (PAG), a brain region shown to be involved in fear circuitry, has a limited body of literature looking at the epigenetic effects associated with aversive early life experiences. The goal of this study was to analyze methylation and expression of BDNF Exon IX in the PAG of rats undergoing a behavioral paradigm in which rat pups are repeatedly exposed to TMT over the first three weeks of life with or without their mother present. The current data suggest that methylation is at least partially responsible for the mechanism behind the change in expression, suggesting the interaction of TMT exposure and maternal separation contributing to this effect. Most importantly, data highlight the susceptibility of the PAG to epigenetic changes as a result of early life experiences, which could yield later changes in offspring fear- and anxiety-like behaviors.