title: Prenatal stress decreases Bdnf expression and increases methylation of Bdnf exon IV in rats.
abstract: There is ample evidence that exposure to stress during gestation increases the risk of the offspring to develop mood disorders. Brain-derived neurotrophic factor (Bdnf) plays a critical role during neuronal development and is therefore a prime candidate to modulate neuronal signaling in adult offspring of rat dams that were stressed during gestation. In the current study, we tested the hypothesis that alterations in Bdnf expression in prenatally stressed (PNS) offspring are mediated by changes in DNA methylation in exons IV and VI of the Bdnf gene. We observed decreased Bdnf expression in the amygdala and hippocampus of prenatally stressed rats both at weaning and in adulthood. This decrease in Bdnf expression was accompanied by increased DNA methylation in Bdnf exon IV in the amygdala and hippocampus, suggesting that PNS-induced reduction in Bdnf expression may, at least in part, be mediated by increased DNA methylation of Bdnf exon IV. Expression of DNA methyltransferases (Dnmt) 1 and 3a was increased in PNS rats in the amygdala and hippocampus. Our data suggest that PNS induces decreases in Bdnf expression that may at least in part be mediated by increased DNA methylation of Bdnf exon IV.
authors.affiliation: Mood Disorders Center; Department of Psychiatry and Behavioral Sciences; Johns Hopkins University; School of Medicine; Baltimore, MD USA.
authors.forename: Gretha J
authors.initials: GJ
authors.lastname: Boersma
authors.affiliation: Mood Disorders Center; Department of Psychiatry and Behavioral Sciences; Johns Hopkins University; School of Medicine; Baltimore, MD USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Lee
authors.affiliation: Mood Disorders Center; Department of Psychiatry and Behavioral Sciences; Johns Hopkins University; School of Medicine; Baltimore, MD USA.
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Cordner
authors.affiliation: Mood Disorders Center; Department of Psychiatry and Behavioral Sciences; Johns Hopkins University; School of Medicine; Baltimore, MD USA.
authors.forename: Erin R
authors.initials: ER
authors.lastname: Ewald
authors.affiliation: Mood Disorders Center; Department of Psychiatry and Behavioral Sciences; Johns Hopkins University; School of Medicine; Baltimore, MD USA.
authors.forename: Ryan H
authors.initials: RH
authors.lastname: Purcell
authors.affiliation: Mood Disorders Center; Department of Psychiatry and Behavioral Sciences; Johns Hopkins University; School of Medicine; Baltimore, MD USA.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Moghadam
authors.affiliation: Mood Disorders Center; Department of Psychiatry and Behavioral Sciences; Johns Hopkins University; School of Medicine; Baltimore, MD USA.
authors.forename: Kellie L
authors.initials: KL
authors.lastname: Tamashiro
mesh_terms: D000679:Amygdala / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D005091:Exons; D005260:Female; D006624:Hippocampus / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D008297:Male; D017397:Prefrontal Cortex / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000235:genetics* / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A
keywords: Bdnf; DMNT; DNA methylation; animal model; epigenetics; prenatal stress