Assessment of caregiver experiences and their association with lasting epigenetic effects on bdnf gene activity within the dorsal and ventral hippocampus
University of Delaware
Current research in the fields of developmental psychology and neuroscience has revealed that there are sensitive periods during postnatal development in which the developing brain has a high level of plasticity, and that early-life caregiving experiences can shape neural circuits and determine the structural and functional aspects of brain and behavior into adulthood and even across generations. These earlylife caregiver experiences produce epigenetic modifications, which are mechanisms that produce functional and heritable changes in the genome without altering the underlying DNA sequence. This is a gene-environment interaction that could influence risk or resiliency to later psychiatric disorders. This study focused on DNA methylation, an epigenetic mechanism that typically blocks and suppresses gene transcription. The stable nature of DNA methylation makes it ideal for determining long-lived gene effects that control brain function and behavior. In particular, this study assessed DNA methylation of the Brain-derived neurotrophic factor (Bdnf) gene, because it continues to be associated with long-term memory, the lasting effects of stress in adulthood, and neuropsychiatric disorders. Previous research with various rodent models suggests that early stress or variations in caregiving alter the expression of both Bdnf mRNA and BDNF protein levels in several regions, including the hippocampus. Regulatory mechanisms facilitating these early-life experience-induced changes are not clear, thus I assessed Bdnf methylation and expression in the dorsal and ventral hippocampi of adult male and female rats with a history of adverse or nurturing caregiving. Biochemistry results demonstrate that exposure to adverse or nurturing caregiving experiences during the first postnatal week of life yield distinct patterns of Bdnf DNA methylation and gene expression patterns within the adult hippocampus. Furthermore, the specific nature of the patterns (i.e. increases or decreases) is dependent upon the animal’s sex and Bdnf gene locus (exon I vs. exon IV).