Long-term daily access to alcohol alters dopamine-related synthesis and signaling proteins in the rat striatum |
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Institution: | 1. The Ottawa Hospital, Ottawa, Ontario, Canada;2. Division of Respirology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada;3. Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada;4. Division of Nephrology, Kidney Research Centre, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada;5. Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Ontario, Canada;6. Division of Infectious Diseases, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada;1. Telemedicine Unit of the University of the State of Amazonas, Brazil;2. Internal Medicine Department of Ascoli Piceno, Marche Region Health District, Italy;3. Marche Region Health District, Italy;4. Birkbeck University of London, United Kingdom;5. Cytopathology Unit, Marche Polytechnic University Hospital, Italy;6. Marche Polytechnic University Hospital, Italy;7. Medical Oncology Unit, Marche Polytechnic University Hospital, Italy;8. Radiology Department, Marche Polytechnic University Hospital, Italy |
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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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