PMID- 30419244
OWN - NLM
STAT- MEDLINE
DCOM- 20200123
LR  - 20210112
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 146
DP  - 2019 Mar 1
TI  - Ethanol and a rapid-acting antidepressant produce overlapping changes in exon 
      expression in the synaptic transcriptome.
PG  - 289-299
LID - S0028-3908(18)30844-X [pii]
LID - 10.1016/j.neuropharm.2018.11.007 [doi]
AB  - Alcohol use disorder (AUD) and major depressive disorder (MDD) are prevalent, 
      debilitating, and highly comorbid disorders. The molecular changes that underlie 
      their comorbidity are beginning to emerge. For example, recent evidence showed 
      that acute ethanol exposure produces rapid antidepressant-like biochemical and 
      behavioral responses. Both ethanol and fast-acting antidepressants block 
      N-methyl-D-aspartate receptor (NMDAR) activity, leading to synaptic changes and 
      long-lasting antidepressant-like behavioral effects. We used RNA sequencing to 
      analyze changes in the synaptic transcriptome after acute treatment with ethanol 
      or the NMDAR antagonist, Ro 25-6981. Ethanol and Ro 25-6981 induced differential, 
      independent changes in gene expression. In contrast with gene-level expression, 
      ethanol and Ro 25-6981 produced overlapping changes in exons, as measured by 
      analysis of differentially expressed exons (DEEs). A prominent overlap in genes 
      with DEEs indicated that changes in exon usage were important for both ethanol 
      and Ro 25-6981 action. Structural modeling provided evidence that ethanol-induced 
      exon expression in the NMDAR1 amino-terminal domain could induce conformational 
      changes and thus alter NMDAR function. These findings suggest that the rapid 
      antidepressant effects of ethanol and NMDAR antagonists reported previously may 
      depend on synaptic exon usage rather than gene expression.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Wolfe, Sarah A
AU  - Wolfe SA
AD  - Committee on the Neurobiology of Addictive Disorders, The Scripps Research 
      Institute, La Jolla, CA, 92037, United States.
FAU - Farris, Sean P
AU  - Farris SP
AD  - Waggoner Center for Alcohol and Addiction Research, Department of Neuroscience, 
      University of Texas at Austin, 2500 Speedway, Austin, TX, 78712, United States.
FAU - Mayfield, Joshua E
AU  - Mayfield JE
AD  - Department of Molecular Biosciences, University of Texas at Austin, 2500 
      Speedway, Austin, TX, 78712, United States.
FAU - Heaney, Chelcie F
AU  - Heaney CF
AD  - Department of Physiology and Pharmacology, Wake Forest University Health 
      Sciences, Medical Center Boulevard, Winston-Salem, NC, 27157-1083, United States.
FAU - Erickson, Emma K
AU  - Erickson EK
AD  - Waggoner Center for Alcohol and Addiction Research, Department of Neuroscience, 
      University of Texas at Austin, 2500 Speedway, Austin, TX, 78712, United States.
FAU - Harris, R Adron
AU  - Harris RA
AD  - Waggoner Center for Alcohol and Addiction Research, Department of Neuroscience, 
      University of Texas at Austin, 2500 Speedway, Austin, TX, 78712, United States.
FAU - Mayfield, R Dayne
AU  - Mayfield RD
AD  - Waggoner Center for Alcohol and Addiction Research, Department of Neuroscience, 
      University of Texas at Austin, 2500 Speedway, Austin, TX, 78712, United States.
FAU - Raab-Graham, Kimberly F
AU  - Raab-Graham KF
AD  - Department of Physiology and Pharmacology, Wake Forest University Health 
      Sciences, Medical Center Boulevard, Winston-Salem, NC, 27157-1083, United States. 
      Electronic address: kraabgra@wakehealth.edu.
LA  - eng
GR  - P50 AA026117/AA/NIAAA NIH HHS/United States
GR  - T32 AA007471/AA/NIAAA NIH HHS/United States
GR  - T32 AA007565/AA/NIAAA NIH HHS/United States
GR  - R01 NS105005/NS/NINDS NIH HHS/United States
GR  - U01 AA013517/AA/NIAAA NIH HHS/United States
GR  - R01 AA026551/AA/NIAAA NIH HHS/United States
GR  - P01 AA020683/AA/NIAAA NIH HHS/United States
GR  - U01 AA020926/AA/NIAAA NIH HHS/United States
GR  - U24 AA013517/AA/NIAAA NIH HHS/United States
GR  - R01 AA012404/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 - 20181109
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Antidepressive Agents)
RN  - 0 (Phenols)
RN  - 0 (Piperidines)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Receptors, Neurotransmitter)
RN  - 0 (Ro 25-6981)
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Alcoholism/*genetics
MH  - Alternative Splicing/drug effects/genetics
MH  - Animals
MH  - Antidepressive Agents/pharmacology
MH  - Comorbidity
MH  - Depressive Disorder, Major/*genetics
MH  - Ethanol/pharmacology
MH  - Exons/*drug effects/*genetics
MH  - Gene Expression/*drug effects
MH  - Hippocampus/drug effects
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Models, Animal
MH  - Phenols/pharmacology
MH  - Piperidines/pharmacology
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors
MH  - Receptors, Neurotransmitter
MH  - Transcriptome
PMC - PMC6778957
MID - NIHMS1007880
OTO - NOTNLM
OT  - Alcohol use disorder
OT  - Alternative splicing
OT  - Differential exon usage
OT  - Major depressive disorder
OT  - Synaptic transcriptome
COIS- Declarations of interest The authors report no biomedical financial interests or 
      potential conflicts of interests.
EDAT- 2018/11/13 06:00
MHDA- 2020/01/24 06:00
PMCR- 2019/10/07
CRDT- 2018/11/13 06:00
PHST- 2018/05/14 00:00 [received]
PHST- 2018/10/03 00:00 [revised]
PHST- 2018/11/07 00:00 [accepted]
PHST- 2018/11/13 06:00 [pubmed]
PHST- 2020/01/24 06:00 [medline]
PHST- 2018/11/13 06:00 [entrez]
PHST- 2019/10/07 00:00 [pmc-release]
AID - S0028-3908(18)30844-X [pii]
AID - 10.1016/j.neuropharm.2018.11.007 [doi]
PST - ppublish
SO  - Neuropharmacology. 2019 Mar 1;146:289-299. doi: 10.1016/j.neuropharm.2018.11.007. 
      Epub 2018 Nov 9.