title: GLAST But Not Least--Distribution, Function, Genetics and Epigenetics of L-Glutamate Transport in Brain--Focus on GLAST/EAAT1.
abstract: 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.
authors.affiliation: Laboratory of Neurobiology and Molecular Psychiatry, Department of Biochemistry, Faculty of Science, Masaryk University, Kotlářská 2, 611 37, Brno, Czech Republic.|Institute of Animal Physiology and Genetics, Academy of Sciences, Veveří 97, 602 00, Brno, Czech Republic.
authors.forename: Omar
authors.initials: O
authors.lastname: Šerý
authors.affiliation: 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.
authors.forename: Nilufa
authors.initials: N
authors.lastname: Sultana
authors.affiliation: 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.
authors.forename: Mohammed Abul
authors.initials: MA
authors.lastname: Kashem
authors.affiliation: School of Medical Sciences, RMIT University, Bundoora, VIC, 3083, Australia.
authors.forename: David V
authors.initials: DV
authors.lastname: Pow
authors.affiliation: 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. vibar@anatomy.usyd.edu.au.
authors.forename: Vladimir J
authors.initials: VJ
authors.lastname: Balcar
mesh_terms: D000437:Alcoholism / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active; D001923:Brain Chemistry / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics* / Q000502:physiology*; D027341:Excitatory Amino Acid Transporter 1 / Q000235:genetics* / Q000378:metabolism*; D050491:Glutamate Plasma Membrane Transport Proteins / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans
chemical_list: D027341:Excitatory Amino Acid Transporter 1; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid
keywords: Alcoholism; DNA methylation; Epigenetics; Ethanol; Glutamate transport; Polymorphisms; miRNA