We report on changes in neurotransmitter metabolome and protein expression in the striatum of humans exposed to heavy long-term consumption of alcohol. Extracts from post mortem striatal tissue (dorsal striatum; DS comprising caudate nucleus; CN and putamen; P and ventral striatum; VS constituted by nucleus accumbens; NAc) were analysed by high performance liquid chromatography coupled with tandem mass spectrometry. Proteomics was studied in CN by two-dimensional gel electrophoresis followed by mass-spectrometry. Proteomics identified 25 unique molecules expressed differently by the alcohol-affected tissue. Two were dopamine-related proteins and one a GABA-synthesizing enzyme GAD65. Two proteins that are related to apoptosis and/or neuronal loss (BiD and amyloid-β A4 precursor protein-binding family B member 3) were increased. There were no differences in the levels of dopamine (DA), 3,4-dihydrophenylacetic acid (DOPAC), serotonin (5HT), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (HIAA), histamine, L-glutamate (Glu), γ-aminobutyric acid (GABA), tyrosine (Tyr) and tryptophan (Tryp) between the DS (CN and P) and VS (NAc) in control brains. Choline (Ch) and acetylcholine (Ach) were higher and norepinephrine (NE) lower, in the VS. Alcoholic striata had lower levels of neurotransmitters except for Glu (30 % higher in the alcoholic ventral striatum). Ratios of DOPAC/DA and HIAA/5HT were higher in alcoholic striatum indicating an increase in the DA and 5HT turnover. Glutathione was significantly reduced in all three regions of alcohol-affected striatum. We conclude that neurotransmitter systems in both the DS (CN and P) and the VS (NAc) were significantly influenced by long-term heavy alcohol intake associated with alcoholism.

Bioanalytical Mass Spectrometry Facility NeuRA NSW University Sydney NSW 2031 Australia

Lab of Neurochemistry Discipline of Anatomy and Histology Bosch Institute for Biomedical Research and School of Medical Sciences Sydney Medical School Anderson Stuart Bldg F13 The University of Sydney Sydney NSW 2006 Australia

Lab of Psychopharmacology School of Psychology The University of Sydney Sydney NSW 2006 Australia

Laboratory of Neurobiology and Molecular Psychiatry Department of Biochemistry Faculty of Science Masaryk University Brno Czech Republic

Neuroscience Research Australia Randwick Sydney NSW 2031 Australia

School of Medical Sciences UNSW Sydney NSW 2052 Australia

Zobrazit více v PubMed

Mol Psychiatry. 2012 Jul;17(7):694-704 PubMed

J Autism Dev Disord. 2012 Feb;42(2):147-60 PubMed

Alcohol Clin Exp Res. 2011 Apr;35(4):756-64 PubMed

J Neurosci. 2013 Apr 10;33(15):6454-9 PubMed

Pharmacol Biochem Behav. 2009 Apr;92(2):304-13 PubMed

Neuron. 2002 Aug 15;35(4):605-23 PubMed

Crit Rev Eukaryot Gene Expr. 1999;9(1):19-32 PubMed

Neurochem Res. 2013 Jul;38(7):1424-33 PubMed

Alcohol Health Res World. 1997;21(2):144-8 PubMed

Neurosci Lett. 2001 Mar 9;300(2):63-6 PubMed

Ann Neurol. 2010 May;67(5):639-47 PubMed

Neuropharmacology. 2012 Nov;63(6):1075-84 PubMed

Gen Hosp Psychiatry. 2012 Nov-Dec;34(6):702.e9-702.e11 PubMed

Neurochem Int. 2007 Jan;50(2):450-9 PubMed

Genet Mol Biol. 2012 Dec;35(4 (suppl)):912-8 PubMed

Annu Rev Neurosci. 2009;32:127-47 PubMed

Brain Res Brain Res Rev. 2000 Mar;31(2-3):205-35 PubMed

Philos Trans R Soc Lond B Biol Sci. 2012 Sep 5;367(1601):2444-59 PubMed

J Pharm Biomed Anal. 2014 Jan;88:416-22 PubMed

Prog Neurobiol. 2010 Nov;92(3):421-41 PubMed

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

J Clin Invest. 2003 May;111(10 ):1444-51 PubMed

J Neurosci. 2004 May 26;24(21):5022-30 PubMed

J Comp Neurol. 2003 Jun 2;460(3):345-67 PubMed

Neuroscience. 1989;31(2):327-45 PubMed

Brain Res Mol Brain Res. 1996 Sep 5;41(1-2):210-5 PubMed

Alcohol. 1985 May-Jun;2(3):415-8 PubMed

Pharmacol Ther. 2005 Oct;108(1):18-58 PubMed

Neurochem Int. 2009 Dec;55(7):483-90 PubMed

Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15254-9 PubMed

Neuroscience. 2014 Mar 14;262:107-17 PubMed

Neuropsychopharmacology. 2010 Mar;35(4):1026-39 PubMed

Pharmacol Biochem Behav. 1982 Jan;16(1):145-9 PubMed

Prog Neuropsychopharmacol Biol Psychiatry. 2005 Dec;29(8):1214-24 PubMed

Biol Psychiatry. 2002 Dec 15;52(12):1151-8 PubMed

Expert Rev Proteomics. 2007 Aug;4(4):539-52 PubMed

Mol Psychiatry. 2004 Jun;9(6):557-69 PubMed

Behav Brain Res. 2012 Jan 1;226(1):224-34 PubMed

Physiol Behav. 2012 Jun 6;106(3):332-6 PubMed

Neurosci Res. 2009 Apr;63(4):267-72 PubMed

J Neurochem. 2009 Jul;110(2):486-95 PubMed

Neuropsychopharmacology. 2010 Jan;35(1):217-38 PubMed

Neurochem Res. 2015 Dec;40(12):2461-72 PubMed

J Neurochem. 2014 Apr;129(2):304-14 PubMed

Neuro Endocrinol Lett. 2006 Feb-Apr;27(1-2):231-5 PubMed

Curr Neuropharmacol. 2007 Sep;5(3):202-12 PubMed

PLoS One. 2012;7(2):e31089 PubMed

Physiol Behav. 2011 Jul 25;104(1):76-81 PubMed

Neuropharmacology. 2014 Feb;77:177-84 PubMed

J Neurol Sci. 1980 Dec;48(3):303-13 PubMed

Curr Top Behav Neurosci. 2013;13:3-30 PubMed

Drug Alcohol Depend. 2012 Aug 1;124(3):200-6 PubMed

Behav Brain Funct. 2011 Dec 31;7:51 PubMed

Nat Rev Neurosci. 2013 Sep;14(9):609-25 PubMed

J Neurosci. 2000 May 1;20(9):3157-64 PubMed

Neurochem Int. 2012 Dec;61(8):1280-8 PubMed

Trends Neurosci. 2004 Nov;27(11):662-9 PubMed

Neuropsychopharmacology. 1996 Jan;14(1):67-76 PubMed

Neurosci Biobehav Rev. 2013 Nov;37(9 Pt A):1946-54 PubMed

Alcohol Clin Exp Res. 2009 Jun;33(6):945-69 PubMed

J Pharm Biomed Anal. 2011 Apr 28;55(1):101-8 PubMed

Psychol Med. 2000 Mar;30(2):443-54 PubMed

Psychiatry Res. 1987 Dec;22(4):291-301 PubMed

Biol Psychiatry. 2012 Jun 1;71(11):1015-21 PubMed

Anal Biochem. 1976 May 7;72:248-54 PubMed

J Neurosci Methods. 2011 Jun 15;198(2):187-94 PubMed

Neurochem Int. 2008 Jul;53(1-2):1-11 PubMed

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

J Neurosci. 2004 Apr 7;24(14):3554-62 PubMed

Neurochem Int. 2007 Nov-Dec;51(6-7):370-6 PubMed

Pharmacol Biochem Behav. 1996 Sep;55(1):141-50 PubMed

J Neurochem. 2005 Dec;95(5):1446-60 PubMed

Alcohol. 1990 May-Jun;7(3):199-205 PubMed

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

Drug Alcohol Depend. 2011 May 1;115(1-2):35-42 PubMed

Mol Psychiatry. 2001 Jan;6(1):109-11 PubMed

Prog Brain Res. 2014;211:141-64 PubMed

Single Nucleotide Polymorphism rs11136000 of CLU Gene (Clusterin, ApoJ) and the Risk of Late-Onset Alzheimer's Disease in a Central European Population