Assessment of caregiver experiences and their association with lasting epigenetic effects on bdnf gene activity within the dorsal and ventral hippocampus
Date
2013-05
Authors
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Journal ISSN
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Publisher
University of Delaware
Abstract
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).