Long-term daily access to alcohol alters dopamine-related synthesis and signaling proteins in the rat striatum |
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Authors: | Mohammed Abul Kashem Selina Ahmed Ranjana SarkerEakhlas U. Ahmed Garth A. HargreavesIain S. McGregor |
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Affiliation: | Psychopharmacology and Proteomics Laboratory, School of Psychology, The University of Sydney, NSW 2006, Australia |
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Abstract: | Chronic alcohol exposure can adversely affect neuronal morphology, synaptic architecture and associated neuroplasticity. However, the effects of moderate levels of long-term alcohol intake on the brain are a matter of debate. The current study used 2-DE (two-dimensional gel electrophoresis) proteomics to examine proteomic changes in the striatum of male Wistar rats after 8 months of continuous access to a standard off-the-shelf beer in their home cages. Alcohol intake under group-housed conditions during this time was around 3–4 g/kg/day, a level below that known to induce physical dependence in rats. After 8 months of access rats were euthanased and 2-DE proteomic analysis of the striatum was conducted. A total of 28 striatal proteins were significantly altered in the beer drinking rats relative to controls. Strikingly, many of these were dopamine (DA)-related proteins, including tyrosine hydroxylase (an enzyme of DA biosynthesis), pyridoxal phosphate phosphatase (a co-enzyme in DA biosynthesis), DA and cAMP regulating phosphoprotein (a regulator of DA receptors and transporters), protein phosphatase 1 (a signaling protein) and nitric oxide synthase (which modulates DA uptake). Selected protein expression changes were verified using Western blotting. We conclude that long-term moderate alcohol consumption is associated with substantial alterations in the rat striatal proteome, particularly with regard to dopaminergic signaling pathways. This provides potentially important evidence of major neuroadaptations in dopamine systems with daily alcohol consumption at relatively modest levels. |
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Keywords: | AC, adenyl cyclase AR, aldose reductase cGMP, cyclic guanylyl monophosphate CREB, cyclic adenosine monophosphate (cAMP) responsive element binding protein DA, dopamine DARPP-32, DA and cAMP regulated phosphoprotein DHAP, converting dihydroxyacetone phosphate eNOS, endothelial nitric oxide synthase G3PDH, glycerol-3-phosphate dehydrogenase GBP, guanine trisphosphate binding protein H2O2, hydrogen peroxide HAD, high alcohol drinking MG, methylglyoxal MST, 3-mercaptopyruvate sulfur transferase NADHD, NADH dehydrogenase NO, nitric oxide NOS, nitric oxide synthase NP, alcohol-non-preferring P, alcohol preferring PP1, protein phosphatase-1 PPP, pentose phosphate pathway PPPase, pyridoxal phosphate phosphatase ROS, reactive oxygen species SOD, superoxide dismutase TCA, tricarboxylic acid cycle TH, tyrosine hydroxylase TPP, tyrosine phosphatase V-ATPase, vacuolar ATPase |
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