Histo- and immunocytochemical detection of inducible NOS and TNF-alpha in the locus coeruleus of human opiate addicts.
In order to determine the role of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of opiate addiction in humans, the expression of both was analyzed in the locus coeruleus (LC) of patients who died from heroin overdose. In control subjects, NADPH-diaphorase (NADPHd) histochemistry was mainly observed in non-noradrenerdic neurons, some glial and endothelial cells. However, in the brain of opiate addicts, NADPHd and iNOS expression was detected in noradrenergic LC cells, correlating with an increase in iNOS and TNF-alpha expression in glial cells as revealed by immunohistochemical and Western blot analyses. These findings indicate that sustained overproduction of cytokine and NO via iNOS expression may be responsible, at least in part, for some neurochemical changes in the locus coeruleus caused by chronic opiate usage in humans.
Dyuizen
I
I
Laboratory of Pharmacology, Institute of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, 17 Palchevskii Str., Vladivostok 690041, Russian Federation. duval@mail.ru
Lamash
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NE
D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D008125:Locus Coeruleus / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009252:NADPH Dehydrogenase / Q000032:analysis / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000378:metabolism*; D009293:Opioid-Related Disorders / Q000378:metabolism* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
D000701:Analgesics, Opioid; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D009252:NADPH Dehydrogenase