Consequences of early-life adversity on the epigenetic landscape of the cerebellar vermis: a role for exercise interventions
Date
2024
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
University of Delaware
Abstract
Individuals who endure adverse caregiving experiences face an elevated risk of experiencing abnormal brain and behavioral development throughout their lives. Negative environmental experiences can lead to epigenetic dysregulation of the Bdnf gene, which encodes brain-derived neurotrophic factor (BDNF). BDNF plays a vital role in early brain development and lifelong health by contributing to processes such as neurogenesis, synaptogenesis, neural plasticity, and cognitive functioning. Disrupted caregiver-infant interactions can result in increased methylation and decreased expression of the Bdnf gene. These epigenetic changes are linked to increased risk of major depressive disorder, anxiety, post-traumatic stress disorder, and substance abuse. This heightened risk of psychopathologies creates a need for therapeutic intervention that may mitigate the epigenetic changes and aberrant behavior. Research has shown that exercise can increase BDNF both at the protein and gene expression levels. Our current project focuses on the impacts of stress and exercise on the vermis of the cerebellum, an understudied region within the field of stress-induced epigenetic regulation. The vermis is a particularly interesting target for understanding the developmental consequences of stress and exercise due to its extended development period and a high concentration of glucocorticoid receptors, making it highly vulnerable to early-life stress. Here we investigated the impact of voluntary wheel running on the abnormal methylation and expression of Bdnf in the cerebellar vermis of adult rats that experienced adverse caregiving during infancy. ANOVA testing showed that infant care condition significantly affected the expression of Bdnf exon IV, with individuals in the maltreatment group exhibiting lower expression compared to the nurturing group. Similarly, infant care had a significant impact on DNA methylation of Bdnf exon IX, with the maltreatment group showing higher methylation levels than the nurturing group. However, we did not find a significant effect of exercise on the expression or methylation of Bdnf. These results are the first to showcase epigenetic regulation of Bdnf occurs in the vermis of the cerebellum following early-life adversity.
Description
Keywords
BDNF gene, Cerebellum, Early-life stress, Epigenetics, Methylation