title: Increased densities of nitric oxide synthase expressing neurons in the temporal cortex and the hypothalamic paraventricular nucleus of polytoxicomanic heroin overdose victims: possible implications for heroin neurotoxicity.
abstract: Heroin is one of the most dangerous drugs of abuse, which may exert various neurotoxic actions on the brain (such as gray matter loss, neuronal apoptosis, mitochondrial dysfunction, synaptic defects, depression of adult neurogenensis, as well as development of spongiform leucoencephalopathy). Some of these toxic effects are probably mediated by the gas nitric oxide (NO). We studied by morphometric analysis the numerical density of neurons expressing neuronal nitric oxide synthase (nNOS) in cortical and hypothalamic areas of eight heroin overdose victims and nine matched controls. Heroin addicts showed significantly increased numerical densities of nNOS immunoreactive cells in the right temporal cortex and the left paraventricular nucleus. Remarkably, in heroin abusers, but not in controls, we observed not only immunostained interneurons, but also cortical pyramidal cells. Given that increased cellular expression of nNOS was accompanied by elevated NO generation in brains of heroin addicts, these elevated levels of NO might have contributed to some of the known toxic effects of heroin (for example, reduced adult neurogenesis, mitochondrial pathology or disturbances in synaptic functioning).
authors: Department of Psychiatry, University of Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany. Electronic address: Hans-Gert.Bernstein@med.ovgu.de.
authors: Hans-Gert
authors: HG
authors: Bernstein
authors: Institute for Legal Medicine, University Essen, Germany.
authors: Kurt
authors: K
authors: Trübner
authors: Department of Psychiatry, University of Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany.
authors: Philipp
authors: P
authors: Krebs
authors: Department of Psychiatry, University of Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany.
authors: Henrik
authors: H
authors: Dobrowolny
authors: Department of Psychiatry, University of Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany.
authors: Hendrik
authors: H
authors: Bielau
authors: Department of Psychiatry, University of Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany.
authors: Johann
authors: J
authors: Steiner
authors: Department of Psychiatry, University of Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany.
authors: Bernhard
authors: B
authors: Bogerts
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D062787:Drug Overdose / Q000201:enzymology* / Q000401:mortality; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D003932:Heroin / Q000506:poisoning*; D006556:Heroin Dependence / Q000201:enzymology* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009294:Narcotics / Q000506:poisoning*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D013702:Temporal Lobe / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology
chemical_list: D009294:Narcotics; D003932:Heroin; D019001:Nitric Oxide Synthase; D005968:Glutamate Decarboxylase; D005974:Glutamate-Ammonia Ligase
keywords: Heroin abuse; Immunohistochemistry; Morphometry; Neuronal nitric oxide synthase; Post-mortem brain