PMID- 33767622
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210925
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - Chronic Voluntary Alcohol Drinking Causes Anxiety-like Behavior, Thiamine 
      Deficiency, and Brain Damage of Female Crossed High Alcohol Preferring Mice.
PG  - 614396
LID - 10.3389/fphar.2021.614396 [doi]
LID - 614396
AB  - The central nervous system is vulnerable to chronic alcohol abuse, and alcohol 
      dependence is a chronically relapsing disorder which causes a variety of physical 
      and mental disorders. Appropriate animal models are important for investigating 
      the underlying cellular and molecular mechanisms. The crossed High Alcohol 
      Preferring mice prefer alcohol to water when given free access. In the present 
      study, we used female cHAP mice as a model of chronic voluntary drinking to 
      evaluate the effects of alcohol on neurobehavioral and neuropathological changes. 
      The female cHAP mice had free-choice access to 10% ethanol and water, while 
      control mice had access to water alone at the age of 60-day-old. The mice were 
      exposed to alcohol for 7 months then subjected to neurobehavioral tests including 
      open field (OF), elevated plus maze (EPM), and Morris water maze (MWM). Results 
      from OF and EPM tests suggested that chronic voluntary drinking caused 
      anxiety-like behaviors. After behavior tests, mice were sacrificed, and brain 
      tissues were processed for biochemical analyses. Alcohol altered the levels of 
      several neurotransmitters and neurotrophic factors in the brain including 
      gamma-Aminobutyric acid (GABA), corticotropin-releasing factor, cAMP response 
      element-binding protein (CREB) and brain-derived neurotrophic factor. Alcohol 
      increased the expression of neuroinflammation markers including interleukin-6 
      (IL-6), tumor necrosis factor alpha (TNF-alpha), monocyte chemoattractant protein-1 
      (MCP-1) and C-C chemokine receptor 2 (CCR2). Alcohol also induced cleaved 
      caspase-3 and glial fibrillary acidic protein, indicative of neurodegeneration 
      and gliosis. In addition, alcohol inhibited the expression of thiamine 
      transporters in the brain and reduced thiamine levels in the blood. Alcohol also 
      caused oxidative stress and endoplasmic reticulum (ER) stress, and stimulated 
      neurogenesis.
CI  - Copyright (c) 2021 Xu, Li, Liu, Wen, Xu, Frank, Chen, Zhu, Grahame and Luo.
FAU - Xu, Hong
AU  - Xu H
AD  - Department of Pharmacology and Nutritional Sciences, University of Kentucky 
      College of Medicine, Lexington, KY, United States.
FAU - Li, Hui
AU  - Li H
AD  - Department of Pathology, University of Iowa Carver College of Medicine, Iowa 
      City, IA, United States.
FAU - Liu, Dexiang
AU  - Liu D
AD  - Department of Medical Psychology, Shandong University School of Medicine, Jinan, 
      China.
FAU - Wen, Wen
AU  - Wen W
AD  - Department of Pathology, University of Iowa Carver College of Medicine, Iowa 
      City, IA, United States.
FAU - Xu, Mei
AU  - Xu M
AD  - Department of Pharmacology and Nutritional Sciences, University of Kentucky 
      College of Medicine, Lexington, KY, United States.
FAU - Frank, Jacqueline A
AU  - Frank JA
AD  - Department of Pharmacology and Nutritional Sciences, University of Kentucky 
      College of Medicine, Lexington, KY, United States.
FAU - Chen, Jing
AU  - Chen J
AD  - Department of Molecular and Cellular Biochemistry, University of Kentucky College 
      of Medicine, Lexington, KY, United States.
FAU - Zhu, Haining
AU  - Zhu H
AD  - Department of Molecular and Cellular Biochemistry, University of Kentucky College 
      of Medicine, Lexington, KY, United States.
FAU - Grahame, Nicholas J
AU  - Grahame NJ
AD  - Department of Psychology, Indiana University-Purdue University Indianapolis, 
      Indianapolis, IN, United States.
FAU - Luo, Jia
AU  - Luo J
AD  - Department of Pathology, University of Iowa Carver College of Medicine, Iowa 
      City, IA, United States.
AD  - Iowa City VA Health Care System, Iowa City, IA, United States.
LA  - eng
GR  - I01 BX001721/BX/BLRD VA/United States
GR  - P60 AA007611/AA/NIAAA NIH HHS/United States
GR  - R01 AA015407/AA/NIAAA NIH HHS/United States
GR  - R01 AA017226/AA/NIAAA NIH HHS/United States
PT  - Journal Article
DEP - 20210309
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC7985542
OTO - NOTNLM
OT  - alcohol use disorder
OT  - endoplasmic reticulum stress
OT  - neurodegeneration
OT  - neuroinflammation
OT  - oxidative stress
COIS- The 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- 2021/03/27 06:00
MHDA- 2021/03/27 06:01
PMCR- 2021/03/09
CRDT- 2021/03/26 06:55
PHST- 2020/10/06 00:00 [received]
PHST- 2021/01/29 00:00 [accepted]
PHST- 2021/03/26 06:55 [entrez]
PHST- 2021/03/27 06:00 [pubmed]
PHST- 2021/03/27 06:01 [medline]
PHST- 2021/03/09 00:00 [pmc-release]
AID - 614396 [pii]
AID - 10.3389/fphar.2021.614396 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Mar 9;12:614396. doi: 10.3389/fphar.2021.614396. 
      eCollection 2021.