The developmental effects of 2,5-dihydro-2,4,5- trimethylthiazoline (TMT) exposure on epigenetic variation in the periaqueductal gray
Date
2023
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Publisher
University of Delaware
Abstract
The presence of a caregiver during aversive situations has the ability to mitigate consequences for later psychopathology. Maternal presence is paramount for proper development, and using a rat model to manipulate caregiver presence in the face of adversity allows for behavioral and biochemical evaluation of underlying mechanisms of this phenomenon. For the current project, Long-Evans rat pups with or without their mother present were exposed to predator odor (TMT) or a control odor (BTA) throughout the first three weeks of life, with subsequent analysis of their brain DNA methylation and gene expression. We focused on DNA methylation and expression of the brain-derived neurotrophic factor (BDNF) gene, as it aids several important aspects of brain development and functioning. Epigenetic changes of the Bdnf gene as a result of TMT exposure and maternal presence were observed in the periaqueductal gray (PAG), a midbrain structure related to fear circuitry and the expression of fear related behaviors. ANOVA testing was utilized to determine significantly altered gene expression and/or methylation, an epigenetic mechanism typically inversely related to gene expression. For gene expression, there were main effects of maternal presence and odor exposure, both producing decreased BdnfIX expression in the PAG. For DNA methylation, there was a significant interaction, with the TMT-no mom group demonstrating the highest levels of methylation. These results are the first to explore developmental epigenetic changes to the PAG and provide further insight into the ability of maternal presence and early adversity to have molecular impacts on the brain.
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Keywords
BDNF gene, Development, Early life adversity, Epigenetics, Maternal presence, Periaqueductal gray