PMID- 31229451
OWN - NLM
STAT- MEDLINE
DCOM- 20200721
LR  - 20231213
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 157
DP  - 2019 Oct
TI  - Altered amygdala DNA methylation mechanisms after adolescent alcohol exposure 
      contribute to adult anxiety and alcohol drinking.
PG  - 107679
LID - S0028-3908(19)30237-0 [pii]
LID - 10.1016/j.neuropharm.2019.107679 [doi]
AB  - Binge drinking during adolescence increases the risk for neuropsychiatric 
      disorders including alcoholism in adulthood. DNA methylation in post-mitotic 
      neurons is an important epigenetic modification that plays a crucial role in 
      neurodevelopment. We examined the effects of intermittent ethanol exposure during 
      adolescence on adult behavior and whether DNA methylation changes provide a 
      plausible explanation for the lasting effects of this developmental insult. One 
      hour after last adolescent intermittent ethanol (AIE), growth arrest and DNA 
      damage inducible protein 45 (Gadd45a, Gadd45b, and Gadd45g) mRNA expression was 
      increased and DNA methyltransferase (DNMT) activity and Dnmt3b expression was 
      decreased in the amygdala as compared to adolescent intermittent saline (AIS) 
      rats. However, AIE rats 24 h after last exposure displayed increased DNMT 
      activity but normalized Gadd45 and Dnmt3b mRNA expression compared to AIS rats. 
      In adulthood, rats exposed to AIE show increased Dnmt3b mRNA expression and DNMT 
      activity, along with decreased Gadd45g mRNA expression in the amygdala. DNA 
      methylation of neuropeptide Y (Npy) and brain-derived neurotrophic factor (Bdnf) 
      exon IV is increased in the AIE adult amygdala compared to AIS adult rats. 
      Treatment with the DNMT inhibitor 5-azacytidine (5-azaC) at adulthood normalizes 
      the AIE-induced DNA hypermethylation of Npy and Bdnf exon IV with concomitant 
      reversal of AIE-induced anxiety-like and alcohol-drinking behaviors. These 
      results suggest that binge-like ethanol exposure during adolescence leads to 
      dysregulation in DNA methylation mechanisms in the amygdala which may contribute 
      to behavioral phenotypes of anxiety and alcohol use in adulthood.
CI  - Published by Elsevier Ltd.
FAU - Sakharkar, Amul J
AU  - Sakharkar AJ
AD  - Center for Alcohol Research in Epigenetics, Department of Psychiatry, University 
      of Illinois at Chicago, Chicago, IL, 60612, USA; Jesse Brown Veterans Affairs 
      Medical Center, Chicago, IL, 60612, USA.
FAU - Kyzar, Evan J
AU  - Kyzar EJ
AD  - Center for Alcohol Research in Epigenetics, Department of Psychiatry, University 
      of Illinois at Chicago, Chicago, IL, 60612, USA; Jesse Brown Veterans Affairs 
      Medical Center, Chicago, IL, 60612, USA.
FAU - Gavin, David P
AU  - Gavin DP
AD  - Center for Alcohol Research in Epigenetics, Department of Psychiatry, University 
      of Illinois at Chicago, Chicago, IL, 60612, USA; Jesse Brown Veterans Affairs 
      Medical Center, Chicago, IL, 60612, USA.
FAU - Zhang, Huaibo
AU  - Zhang H
AD  - Center for Alcohol Research in Epigenetics, Department of Psychiatry, University 
      of Illinois at Chicago, Chicago, IL, 60612, USA; Jesse Brown Veterans Affairs 
      Medical Center, Chicago, IL, 60612, USA.
FAU - Chen, Ying
AU  - Chen Y
AD  - Center for Alcohol Research in Epigenetics, Department of Psychiatry, University 
      of Illinois at Chicago, Chicago, IL, 60612, USA.
FAU - Krishnan, Harish R
AU  - Krishnan HR
AD  - Center for Alcohol Research in Epigenetics, Department of Psychiatry, University 
      of Illinois at Chicago, Chicago, IL, 60612, USA; Jesse Brown Veterans Affairs 
      Medical Center, Chicago, IL, 60612, USA.
FAU - Grayson, Dennis R
AU  - Grayson DR
AD  - Center for Alcohol Research in Epigenetics, Department of Psychiatry, University 
      of Illinois at Chicago, Chicago, IL, 60612, USA.
FAU - Pandey, Subhash C
AU  - Pandey SC
AD  - Center for Alcohol Research in Epigenetics, Department of Psychiatry, University 
      of Illinois at Chicago, Chicago, IL, 60612, USA; Department of Anatomy and Cell 
      Biology, University of Illinois at Chicago, Chicago, IL, 60612, USA; Jesse Brown 
      Veterans Affairs Medical Center, Chicago, IL, 60612, USA. Electronic address: 
      scpandey@uic.edu.
LA  - eng
GR  - F30 AA024948/AA/NIAAA NIH HHS/United States
GR  - R01 AA010005/AA/NIAAA NIH HHS/United States
GR  - U24 AA024605/AA/NIAAA NIH HHS/United States
GR  - R01 AA025035/AA/NIAAA NIH HHS/United States
GR  - P50 AA022538/AA/NIAAA NIH HHS/United States
GR  - IK2 BX001650/BX/BLRD VA/United States
GR  - I01 BX000143/BX/BLRD VA/United States
GR  - I01 BX004091/BX/BLRD VA/United States
GR  - U01 AA019971/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20190620
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Bdnf protein, rat)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Gadd45a protein, rat)
RN  - 0 (Gadd45b protein, rat)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Neuropeptide Y)
RN  - 3K9958V90M (Ethanol)
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1)
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases)
RN  - EC 2.1.1.37 (Dnmt1 protein, rat)
RN  - M801H13NRU (Azacitidine)
SB  - IM
MH  - Age Factors
MH  - Alcohol Drinking/*physiopathology
MH  - Amygdala/*metabolism
MH  - Animals
MH  - Antigens, Differentiation/biosynthesis
MH  - Anxiety/chemically induced/*physiopathology
MH  - Azacitidine/pharmacology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Cycle Proteins/biosynthesis
MH  - DNA (Cytosine-5-)-Methyltransferase 1/metabolism
MH  - DNA (Cytosine-5-)-Methyltransferases/biosynthesis
MH  - DNA Methylation/*physiology
MH  - Ethanol/antagonists & inhibitors/*pharmacology
MH  - Exons/drug effects
MH  - Intracellular Signaling Peptides and Proteins/biosynthesis
MH  - Male
MH  - Neuropeptide Y/metabolism
MH  - Rats
MH  - DNA Methyltransferase 3B
MH  - GADD45 Proteins
PMC - PMC6681823
MID - NIHMS1039920
OTO - NOTNLM
OT  - Adolescent binge drinking
OT  - Alcohol use disorders
OT  - Amygdala
OT  - Anxiety
OT  - BDNF
OT  - DNA methylation/demethylation
OT  - Neuropeptide Y
COIS- Conflict of interest Authors declare that the research was conducted in the 
      absence of any commercial or financial relationships that could be construed as a 
      potential conflict of interest.
EDAT- 2019/06/24 06:00
MHDA- 2020/07/22 06:00
PMCR- 2020/10/01
CRDT- 2019/06/24 06:00
PHST- 2018/12/04 00:00 [received]
PHST- 2019/06/08 00:00 [revised]
PHST- 2019/06/18 00:00 [accepted]
PHST- 2019/06/24 06:00 [pubmed]
PHST- 2020/07/22 06:00 [medline]
PHST- 2019/06/24 06:00 [entrez]
PHST- 2020/10/01 00:00 [pmc-release]
AID - S0028-3908(19)30237-0 [pii]
AID - 10.1016/j.neuropharm.2019.107679 [doi]
PST - ppublish
SO  - Neuropharmacology. 2019 Oct;157:107679. doi: 10.1016/j.neuropharm.2019.107679. 
      Epub 2019 Jun 20.