Lasting epigenetic influence of early-life adversity on the BDNF gene.
BACKGROUND
Childhood maltreatment and early trauma leave lasting imprints on neural mechanisms of cognition and emotion. With 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 central nervous system.


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.
Roth
Tania L
TL
Department of Neurobiology and the Evelyn F. McKnight Brain Institute, University of Alabama-Birmingham, Birmingham, Alabama 35294, USA.
Lubin
Farah D
FD
Funk
Adam J
AJ
Sweatt
J David
JD
D000818:Animals; D000831:Animals, Newborn / Q000235:genetics* / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism*; D003562:Cytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D019175:DNA Methylation / Q000187:drug effects; D044127:Epigenesis, Genetic; D005260:Female; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D008425:Maternal Behavior; D023421:Models, Animal; D017397:Prefrontal Cortex / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D013315:Stress, Psychological / Q000235:genetics*
D019208:Brain-Derived Neurotrophic Factor; D003562:Cytidine; C009131:pyrimidin-2-one beta-ribofuranoside