title: Adolescent alcohol exposure alters lysine demethylase 1 (LSD1) expression and histone methylation in the amygdala during adulthood.
abstract: Alcohol exposure in adolescence is an important risk factor for the development of alcoholism in adulthood. Epigenetic processes are implicated in the persistence of adolescent alcohol exposure-related changes, specifically in the amygdala. We investigated the role of histone methylation mechanisms in the persistent effects of adolescent intermittent ethanol (AIE) exposure in adulthood. Adolescent rats were exposed to 2 g/kg ethanol (2 days on/off) or intermittent n-saline (AIS) during postnatal days (PND) 28-41 and used for behavioral and epigenetic studies. We found that AIE exposure caused a long-lasting decrease in mRNA and protein levels of lysine demethylase 1(Lsd1) and mRNA levels of Lsd1 + 8a (a neuron-specific splice variant) in specific amygdaloid structures compared with AIS-exposed rats when measured at adulthood. Interestingly, AIE increased histone H3 lysine 9 dimethylation (H3K9me2) levels in the central nucleus of the amygdala (CeA) and medial nucleus of the amygdala (MeA) in adulthood without producing any change in H3K4me2 protein levels. Acute ethanol challenge (2 g/kg) in adulthood attenuated anxiety-like behaviors and the decrease in Lsd1 + 8a mRNA levels in the amygdala induced by AIE. AIE caused an increase in H3K9me2 occupancy at the brain-derived neurotrophic factor exon IV promoter in the amygdala that returned to baseline after acute ethanol challenge in adulthood. These results indicate that AIE specifically modulates epizymes involved in H3K9 dimethylation in the amygdala in adulthood, which are possibly responsible for AIE-induced chromatin remodeling and adult psychopathology such as anxiety.
authors.affiliation: Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA.|Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA.
authors.forename: Evan J
authors.initials: EJ
authors.lastname: Kyzar
authors.affiliation: Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA.|Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA.
authors.forename: Huaibo
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA.|Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA.
authors.forename: Amul J
authors.initials: AJ
authors.lastname: Sakharkar
authors.affiliation: Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA.|Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA.|Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Pandey
mesh_terms: D000367:Age Factors; D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001007:Anxiety; D001522:Behavior, Animal / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D066274:Central Amygdaloid Nucleus / Q000187:drug effects / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D066276:Corticomedial Nuclear Complex / Q000187:drug effects / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D042421:Histone Code / Q000187:drug effects*; D056466:Histone Demethylases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008745:Methylation / Q000187:drug effects*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002492:Central Nervous System Depressants; D006657:Histones; D012333:RNA, Messenger; D000431:Ethanol; D056466:Histone Demethylases; C557089:KDM1A protein, rat
keywords: alcohol; amygdala; anxiety; epigenetics; histone demethylase; histone methylation; lysine demethylase 1