title: Global and gene-specific DNA methylation alterations in the adolescent amygdala and hippocampus in an animal model of caregiver maltreatment.
abstract: Epigenetic mechanisms such as DNA methylation are part of an emerging story on how early-life experiences can alter behavioral trajectories and lead to the development of disease and psychological disorders. Previous work from our laboratory has demonstrated alterations in methylation of DNA associated with the brain-derived neurotrophic factor (bdnf) gene within the amygdala and hippocampus of infant and adult rats that were repeatedly exposed to caregiver maltreatment outside the home cage during their first week of life. In the current study we examine changes in global levels of DNA methylation (5-mC) and hydroxymethylation (5-hmC), as well as gene-specific changes in methylation patterns of the candidate gene bdnf (at exons I and IV) within the adolescent amygdala and hippocampus resulting from exposure to maltreatment. While adolescent females exposed to maltreatment showed no significant alterations in global 5-mC or 5-hmC levels, examination of bdnf DNA methylation revealed that maltreated females had greater methylation of exon IV DNA in the amygdala and ventral hippocampus. While adolescent males exposed to maltreatment showed no significant alterations in bdnf DNA methylation, maltreated males had significantly higher 5-mC levels in the dorsal hippocampus and lower 5-hmC levels in the amygdala. These findings demonstrate that the effects of the early caregiving environment are detectable in the adolescent brain at the level of the epigenome, with brain-region specific and sexually-dimorphic epigenetic consequences that could have relevance to adolescent mental health and behavior.
authors.affiliation: Department of Psychological and Brain Sciences, University of Delaware, 108 Wolf Hall, Newark, DE 19716, United States.
authors.forename: Tiffany S
authors.initials: TS
authors.lastname: Doherty
authors.affiliation: Department of Psychological and Brain Sciences, University of Delaware, 108 Wolf Hall, Newark, DE 19716, United States.
authors.forename: Amy
authors.initials: A
authors.lastname: Forster
authors.affiliation: Department of Psychological and Brain Sciences, University of Delaware, 108 Wolf Hall, Newark, DE 19716, United States. Electronic address: troth@psych.udel.edu.
authors.forename: Tania L
authors.initials: TL
authors.lastname: Roth
mesh_terms: D000679:Amygdala / Q000254:growth & development / Q000378:metabolism*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002649:Child Abuse; D019175:DNA Methylation; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D005091:Exons; D005260:Female; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism*; D006799:Housing, Animal; D006801:Humans; D008297:Male; D008425:Maternal Behavior / Q000523:psychology; D020318:Rats, Long-Evans; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: Adolescence; Bdnf gene; DNA hydroxymethylation; DNA methylation; Early-life stress