Synaptically released L-glutamate, the most important excitatory neurotransmitter in the CNS, is removed from extracellular space by fast and efficient transport mediated by several transporters; the most abundant ones are EAAT1/GLAST and EAAT2/GLT1. The review first summarizes their location, functions and basic characteristics. We then look at genetics and epigenetics of EAAT1/GLAST and EAAT2/GLT1 and perform in silico analyses of their promoter regions. There is one CpG island in SLC1A2 (EAAT2/GLT1) gene and none in SLC1A3 (EAAT1/GLAST) suggesting that DNA methylation is not the most important epigenetic mechanism regulating EAAT1/GLAST levels in brain. There are targets for specific miRNA in SLC1A2 (EAAT2/GLT1) gene. We also note that while defects in EAAT2/GLT1 have been associated with various pathological states including chronic neurodegenerative diseases, very little is known on possible contributions of defective or dysfunctional EAAT1/GLAST to any specific brain disease. Finally, we review evidence of EAAT1/GLAST involvement in mechanisms of brain response to alcoholism and present some preliminary data showing that ethanol, at concentrations which may be reached following heavy drinking, can have an effect on the distribution of EAAT1/GLAST in cultured astrocytes; the effect is blocked by baclofen, a GABA-B receptor agonist and a drug potentially useful in the treatment of alcoholism. We argue that more research effort should be focused on EAAT1/GLAST, particularly in relation to alcoholism and drug addiction.

Institute of Animal Physiology and Genetics Academy of Sciences Veveří 97 602 00 Brno Czech Republic

Laboratory of Neurobiology and Molecular Psychiatry Department of Biochemistry Faculty of Science Masaryk University Kotlářská 2 611 37 Brno Czech Republic

Laboratory of Neurochemistry Bosch Institute and Discipline of Anatomy and Histology School of Medical Sciences Sydney Medical School The University of Sydney Sydney NSW 2006 Australia

School of Medical Sciences RMIT University Bundoora VIC 3083 Australia

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Pharmacol Ther. 2005 Sep;107(3):271-85 PubMed

Int J Clin Pract. 2006 Aug;60(8):1003-8 PubMed

J Neurochem. 1999 Jan;72(1):129-38 PubMed

J Neurosci. 1999 Dec 15;19(24):10767-77 PubMed

Psychopharmacology (Berl). 2013 Oct;229(3):539-54 PubMed

Biol Pharm Bull. 2002 Mar;25(3):291-301 PubMed

Nature. 1996 Oct 17;383(6601):634-7 PubMed

J Biol Chem. 2013 Jul 12;288(28):20195-207 PubMed

Neuroscience. 2008 Nov 11;157(1):80-94 PubMed

Clin Exp Pharmacol Physiol. 2002 Nov;29(11):1018-23 PubMed

J Neurosci Res. 2015 Jul;93(7):1031-44 PubMed

Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):12161-6 PubMed

FEBS Lett. 1992 Apr 6;300(3):203-7 PubMed

Schizophr Res. 2013 Mar;144(1-3):1-8 PubMed

J Neurosci Res. 1998 Dec 1;54(5):595-603 PubMed

J Biol Chem. 2008 May 9;283(19):13116-23 PubMed

J Physiol. 2006 Dec 1;577(Pt 2):591-9 PubMed

Mol Psychiatry. 2001 Jul;6(4):380-6 PubMed

Nat Neurosci. 2006 Nov;9(11):1388-96 PubMed

Mol Vis. 2011 Mar 25;17:792-6 PubMed

J Stud Alcohol. 1999 May;60(3):400-6 PubMed

Eur J Hum Genet. 2015 Sep;23(9):1200-6 PubMed

Methods Cell Biol. 2003;71:89-109 PubMed

Glia. 2012 Sep;60(9):1345-55 PubMed

Asian J Androl. 2011 Mar;13(2):254-65 PubMed

Neuro Endocrinol Lett. 2014;35(5):359-66 PubMed

J Neurochem. 2014 Mar;128(5):641-9 PubMed

Neuroscience. 2013 Dec 19;254:335-46 PubMed

Prog Neurobiol. 2001 Sep;65(1):1-105 PubMed

Nucleic Acids Res. 2013 Dec;41(22):e203 PubMed

J Cell Physiol. 2012 Feb;227(2):596-603 PubMed

Anat Embryol (Berl). 2006 Nov;211(6):595-606 PubMed

Lancet Neurol. 2014 Nov;13(11):1083-1091 PubMed

Arch Biochem Biophys. 1998 May 15;353(2):356-64 PubMed

Mol Pharmacol. 2013 Oct;84(4):603-14 PubMed

J Biol Chem. 2013 Mar 8;288(10 ):7105-16 PubMed

J Neurochem. 2014 Nov;131(4):399-406 PubMed

Neuroscience. 2009 Dec 15;164(3):1068-83 PubMed

Int J Biochem Cell Biol. 2010 Dec;42(12):1901-6 PubMed

Biol Psychiatry. 2005 Jun 1;57(11):1461-6 PubMed

Cell. 2015 Jan 29;160(3):542-53 PubMed

Nature. 2005 Jan 6;433(7021):73-7 PubMed

Clin Exp Pharmacol Physiol. 2004 Nov;31(11):762-9 PubMed

Nucleic Acids Res. 2014 Jan;42(Database issue):D68-73 PubMed

Am J Med Genet B Neuropsychiatr Genet. 2007 Apr 5;144B(3):271-8 PubMed

Neurology. 2014 Mar 18;82(11):1000-7 PubMed

Science. 2008 Apr 25;320(5875):539-43 PubMed

Curr Opin Pharmacol. 2015 Feb;20:116-23 PubMed

J Neurosci Res. 2007 Feb 1;85(2):342-50 PubMed

Glia. 2007 May;55(7):663-74 PubMed

J Neurosci Res. 2000 Mar 1;59(5):587-93 PubMed

Anat Embryol (Berl). 1998 Jul;198(1):13-30 PubMed

Br J Pharmacol. 2007 Jan;150(1):5-17 PubMed

Neuron Glia Biol. 2006 Aug;2(3):199-215 PubMed

Eur J Pharmacol. 1999 Oct 8;382(2):139-42 PubMed

J Neurosci. 2015 Apr 1;35(13):5187-201 PubMed

Mol Autism. 2014 Jul 30;5:40 PubMed

Psychiatr Genet. 2009 Jun;19(3):134-41 PubMed

Neuropharmacology. 2012 Aug;63(2):181-9 PubMed

Pflugers Arch. 2014 Jan;466(1):3-24 PubMed

J Neurosci. 1999 Dec 1;19(23):10193-200 PubMed

J Neural Transm (Vienna). 2014 Aug;121(8):799-817 PubMed

J Biomed Sci. 2005 Dec;12(6):975-84 PubMed

Neurochem Res. 2009 Oct;34(10):1767-74 PubMed

Neurochem Int. 2012 Sep;61(4):566-74 PubMed

N Engl J Med. 1992 May 28;326(22):1464-8 PubMed

Neurology. 2005 Aug 23;65(4):529-34 PubMed

J Histochem Cytochem. 2012 Feb;60(2):139-51 PubMed

J Neurochem. 2002 Jan;80(1):1-11 PubMed

J Neurochem. 2003 Aug;86(3):635-45 PubMed

Biochemistry. 2011 Jun 28;50(25):5558-65 PubMed

Science. 1997 Jun 13;276(5319):1699-702 PubMed

J Neurochem. 2003 Apr;85(2):503-14 PubMed

Neuroscience. 2007 Oct 26;149(2):434-45 PubMed

J Chem Neuroanat. 2012 Jan;43(1):64-75 PubMed

Glia. 2005 Feb;49(3):451-5 PubMed

J Neurochem. 1997 Nov;69(5):2132-7 PubMed

EMBO Mol Med. 2013 Oct;5(10 ):1613-34 PubMed

Neurochem Res. 2009 Oct;34(10):1758-66 PubMed

Neurochem Res. 2010 Dec;35(12):2062-9 PubMed

Am J Med Genet B Neuropsychiatr Genet. 2009 Jan 5;150B(1):95-103 PubMed

Biophys J. 2002 Jul;83(1):125-34 PubMed

J Neurochem. 2005 Oct;95(2):341-8 PubMed

J Neurosci Res. 2003 Dec 15;74(6):956-66 PubMed

Neurochem Int. 2007 Nov-Dec;51(6-7):333-55 PubMed

Neuromolecular Med. 2014 Sep;16(3):565-77 PubMed

J Neurosci. 2013 Oct 30;33(44):17429-34 PubMed

Neuroscience. 2014 Sep 26;277:522-40 PubMed

J Neurosci. 2004 Feb 4;24(5):1136-48 PubMed

Neuropsychopharmacology. 2015 Jun;40(7):1569-79 PubMed

Neuroscience. 1993 Nov;57(1):97-111 PubMed

CNS Neurol Disord Drug Targets. 2010 Mar;9(1):33-44 PubMed

J Neurochem. 1984 Jan;42(1):1-11 PubMed

Nature. 1995 Jun 15;375(6532):599-603 PubMed

Alcohol Clin Exp Res. 2008 Oct;32(10):1849-58 PubMed

Neurochem Res. 2002 Feb;27(1-2):27-35 PubMed

J Endocrinol. 2004 May;181(2):233-44 PubMed

Eur J Neurosci. 1998 Mar;10(3):976-88 PubMed

J Chem Neuroanat. 2012 Jan;43(1):52-63 PubMed

Physiol Rev. 2013 Oct;93(4):1621-57 PubMed

Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3740-5 PubMed

Neuroscience. 2007 Mar 16;145(2):579-91 PubMed

FASEB J. 2002 Jan;16(1):27-35 PubMed

J Neurosci Res. 2010 May 1;88(6):1234-41 PubMed

Physiol Rev. 2009 Apr;89(2):649-705 PubMed

Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1604-9 PubMed

J Biol Chem. 2007 Oct 5;282(40):29414-23 PubMed

Behav Brain Funct. 2011 Jun 28;7:22 PubMed

Eur J Histochem. 2013 Mar 12;57(1):e11 PubMed

Arch Neurol. 2009 Jan;66(1):97-101 PubMed

J Physiol. 2006 Nov 15;577(Pt 1):221-34 PubMed

Cereb Cortex. 2002 May;12(5):515-25 PubMed

Neuroscience. 2001;108(1):51-9 PubMed

J Neurosci. 1998 Dec 1;18(23):9620-8 PubMed

Nat Med. 2005 Jan;11(1):35-42 PubMed

Annu Rev Med. 1998;49:173-84 PubMed

Neurosci Lett. 2011 Jul 25;499(3):154-7 PubMed

Front Neuroanat. 2011 Jan 14;4:151 PubMed

Neurochem Int. 1999 Oct;35(4):269-80 PubMed

Exp Neurol. 2003 Sep;183(1):124-35 PubMed

Cell Mol Neurobiol. 2012 May;32(4):539-47 PubMed

Exp Anim. 2010;59(4):449-57 PubMed

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