title: Exposure to caregiver maltreatment alters expression levels of epigenetic regulators in the medial prefrontal cortex.
abstract: Quality of maternal care experienced during infancy is a key factor that can confer vulnerability or resilience to psychiatric disorders later in life. Research continues to indicate that early-life experiences can affect developmental trajectories through epigenetic alterations capable of affecting gene regulation and neural plasticity. Previously, our lab has shown that experiences within an adverse caregiving environment (i.e. maltreatment) produce aberrant DNA methylation patterns at various gene loci in the medial prefrontal cortex (mPFC) of developing and adult rats. This study aimed to determine whether caregiver maltreatment likewise affects expression levels of several genes important in regulating DNA methylation patterns (Dnmt1, Dnmt3a, MeCP2, Gadd45b, and Hdac1). While we observed minimal changes in gene expression within the mPFC of developing rats, we observed expression changes for all genes in adult animals. Specifically, exposure to maltreatment produced a significant decrease in mRNA levels of all epigenetic regulators in adult males and a significant decrease in Gadd45b in adult females. Our results here provide further empirical support for the long-term and sex-specific epigenetic consequences of caregiver maltreatment on the mPFC.
authors.affiliation: Department of Psychology, University of Delaware, Newark, DE 19716, United States.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Blaze
authors.forename: Tania L
authors.initials: TL
authors.lastname: Roth
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000943:Antigens, Differentiation; D017028:Caregivers / Q000523:psychology; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D034281:Dynamins; D044127:Epigenesis, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D056284:Histone Deacetylase 1; D008297:Male; D051783:Methyl-CpG-Binding Protein 2; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D000097642:GADD45 Proteins
chemical_list: D000943:Antigens, Differentiation; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D034281:Dynamins; D056284:Histone Deacetylase 1; D051783:Methyl-CpG-Binding Protein 2; C508094:Gadd45b protein, rat; D000097642:GADD45 Proteins; C497394:Mecp2 protein, rat; C515890:Hdac1 protein, rat; C519851:Dnm1l protein, rat
keywords: Bdnf; DNA methyltransferase; DNMT; Dnmt; Early-life stress; Epigenetics; Gadd45b; Growth Arrest and DNA-Damage-Inducible beta; HAT; HDAC; Hdac; Maternal care; MeCP2; Methyl-CpG Binding Protein-2; PN; brain-derived neurotrophic factor; histone acetyltransferase; histone deacetylase; mPFC; medial prefrontal cortex; postnatal day