Document Detail


Striatal adenosine signaling regulates EAAT2 and astrocytic AQP4 expression and alcohol drinking in mice.
MedLine Citation:
PMID:  23032072     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adenosine signaling is implicated in several neuropsychiatric disorders, including alcoholism. Among its diverse functions in the brain, adenosine regulates glutamate release and has an essential role in ethanol sensitivity and preference. However, the molecular mechanisms underlying adenosine-mediated glutamate signaling in neuroglial interaction remain elusive. We have previously shown that mice lacking the ethanol-sensitive adenosine transporter, type 1 equilibrative nucleoside transporter (ENT1), drink more ethanol compared with wild-type mice and have elevated striatal glutamate levels. In addition, ENT1 inhibition or knockdown reduces glutamate transporter expression in cultured astrocytes. Here, we examined how adenosine signaling in astrocytes contributes to ethanol drinking. Inhibition or deletion of ENT1 reduced the expression of type 2 excitatory amino-acid transporter (EAAT2) and the astrocyte-specific water channel, aquaporin 4 (AQP4). EAAT2 and AQP4 colocalization was also reduced in the striatum of ENT1 null mice. Ceftriaxone, an antibiotic compound known to increase EAAT2 expression and function, elevated not only EAAT2 but also AQP4 expression in the striatum. Furthermore, ceftriaxone reduced ethanol drinking, suggesting that ENT1-mediated downregulation of EAAT2 and AQP4 expression contributes to excessive ethanol consumption in our mouse model. Overall, our findings indicate that adenosine signaling regulates EAAT2 and astrocytic AQP4 expressions, which control ethanol drinking in mice.
Authors:
Moonnoh R Lee; Christina L Ruby; David J Hinton; Sun Choi; Chelsea A Adams; Na Young Kang; Doo-Sup Choi
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-03
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  38     ISSN:  1740-634X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-16     Completed Date:  2013-10-17     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  England    
Other Details:
Languages:  eng     Pagination:  437-45     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenosine / physiology*
Alcohol Drinking / genetics,  metabolism*,  physiopathology
Animals
Aquaporin 4 / antagonists & inhibitors,  biosynthesis*
Astrocytes / pathology,  physiology*
Cell Line
Corpus Striatum / metabolism*,  physiopathology
Down-Regulation / genetics
Excitatory Amino Acid Transporter 2 / antagonists & inhibitors,  biosynthesis*
Mice
Mice, 129 Strain
Mice, Inbred C57BL
Mice, Knockout
Signal Transduction / genetics
Grant Support
ID/Acronym/Agency:
AA015164/AA/NIAAA NIH HHS; AA018779/AA/NIAAA NIH HHS; R01 AA015164/AA/NIAAA NIH HHS; R01 AA018779/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Aqp4 protein, mouse; 0/Aquaporin 4; 0/Excitatory Amino Acid Transporter 2; 0/Slc1a2 protein, mouse; K72T3FS567/Adenosine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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