LASTING EPIGENETIC INFLUENCE OF EARLY-LIFE ADVERSITY ON THE BDNF GENE

By T. Roth, F. Lubin, A. Funk, J. Sweatt. Biological Psychiatry, 2009

1,263 citations recorded by the source corpus.

Background Childhood maltreatment and early trauma leave lasting imprints on neural mechanisms of cognition and emotion. Using a rat model of infant maltreatment by a caregiver, we investigated whether early-life adversity leaves lasting epigenetic marks at the Brain-derived Neurotrophic Factor (BDNF) gene in the CNS. Methods During the first postnatal week, we exposed infant rats to stressed caretakers that predominately displayed abusive behaviors. We then assessed DNA methylation patterns and gene expression throughout the life span, as well as DNA methylation patterns in the next generation of infants. Results Early maltreatment produced persisting changes in methylation of BDNF DNA that caused altered BDNF gene expression in the adult prefrontal cortex. Furthermore, we observed altered BDNF DNA methylation in offspring of females that had previously experienced the maltreatment regimen. Conclusions These results highlight an epigenetic molecular mechanism potentially underlying lifelong and transgenerational perpetuation of changes in gene expression and behavior incited by early abuse and neglect.

Subfields: Behavioral Neuroscience, Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/73b25ed907cfc11b7dfd5f2e6c7e3f05afbe7148

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Citations in the corpus

Research review: the neurobiology and genetics of maltreatment and adversity. (2010, background): “Roth et al. (2009) also observed altered BDNF DNA methylation in the offspring of these females that had previously been exposed to maltreatment as pups.”
Potential therapeutic uses of BDNF in neurological and psychiatric disorders (2011, background): “In rats, early stress experiences can produce long-term changes in BDNF expression through DNA methylatio”
Epigenetics and the biological definition of gene x environment interactions. (2010, background): “Manipulations that alter mother–pup interactions in the rat alter patterns of gene expression and stress response in the offspring (e.g., Francis et al., 1999; Meaney, 2001; Roth et al., 2009; Toki et al., 2007).”
“The Biological Effects of Childhood Trauma” (2014, positive): “In a rodent model of infant maltreatment, abuse and neglect during infancy decreases brain-derived neurotrophic factor (BDNF) gene expression in the adult PFC.(109) In addition, these investigators found that chronic treatment with a DNA methylation inhibitor lowered levels of methylation in male an”
Maternal adversity and ecological stressors in natural populations: the role of stress axis programming in individuals, with implications for populations and communities (2013, background): “A number of other groups have also found evidence of epigenetic regulation in the brain by altered parental care or stress-related early adversity (e.g. Murgatroyd et al. 2009; Roth et al. 2009).”
Adverse childhood experiences and life opportunities: Shifting the narrative (2017, neutral): “…factors that impact early brain development (McCrory, De Brito, & Viding, 2011; Shonkoff, Boyce, & McEwen, 2009; Shonkoff & Garner, 2012; Danese et al., 2008), the immune system (Bierhaus et al., 2003), and the endocrine system (Colborn, 2004; Roth, Lubin, Funk, & Sweatt, 2009; Szyf, 2009).”
The Role of Early Life Stress as a Predictor for Alcohol and Drug Dependence (2010, background): “Early maltreatment in rats produces persisting changes in methylation of BDNF DNA that results in altered BDNF gene expression in the adult prefrontal cortex (Roth et al. 2009).”