Increased MCP-1 and microglia in various regions of the human alcoholic brain.
Cytokines and microglia have been implicated in anxiety, depression, neurodegeneration as well as the regulation of alcohol drinking and other consumatory behaviors, all of which are associated with alcoholism. Studies using animal models of alcoholism suggest that microglia and proinflammatory cytokines contribute to alcoholic pathologies [Crews, F.T., Bechara, R., Brown, L.A., Guidot, D.M., Mandrekar, P., Oak, S., Qin, L., Szabo, G., Wheeler, M., Zou, J., (2006) Cytokines and alcohol. Alcohol., Clin. Exp. Res. 30:720-730]. In the current study, human postmortem brains from moderate drinking controls and alcoholics obtained from the New South Wales Tissue Resource Center were used to study the cytokine, monocyte chemoattractant protein 1 (MCP-1,CCL2) and microglia markers in various brain regions. Since MCP-1 is a key proinflammatory cytokine induced by chronic alcohol treatment of mice, and known to regulate drinking behavior in mice, MCP-1 protein levels from human brain homogenate were measured using ELISA, and indicated increased MCP-1 concentration in ventral tegmental area (VTA), substantia nigra (SN), hippocampus and amygdala of alcoholic brains as compared with controls. Immunohistochemistry was further performed to visualize human microglia using ionized calcium binding adaptor protein-1 (Iba-1), and Glucose transporter-5 (GluT5). Alcoholics were found to have brain region-specific increases in microglial markers. In cingulate cortex, both Iba-1 and GluT5 were increased in alcoholic brains relative to controls. Alternatively, no detectable change was found in amygdala nuclei. In VTA and midbrain, only GluT5, but not Iba-1 was increased in alcoholic brains. These data suggest that the enhanced expression of MCP-1 and microglia activities in alcoholic brains could contribute to ethanol-induced pathogenesis.
He
Jun
J
Bowles Center for Alcohol Studies, Department of Pharmacology and Psychiatry, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7178, USA. junhe@med.unc.edu
Crews
Fulton T
FT
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000473:pathology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D002135:Calcium-Binding Proteins; D018932:Chemokine CCL2 / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D051296:Glucose Transporter Type 5 / Q000378:metabolism; D006801:Humans; D008297:Male; D008840:Microfilament Proteins; D017628:Microglia / Q000473:pathology*; D008875:Middle Aged; D011180:Postmortem Changes
C112986:AIF1 protein, human; C111835:CCL2 protein, human; D002135:Calcium-Binding Proteins; D018932:Chemokine CCL2; D004268:DNA-Binding Proteins; D051296:Glucose Transporter Type 5; D008840:Microfilament Proteins; C495726:SLC2A5 protein, human