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.
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).
['Bernstein|Hans-Gert|HG|', 'Trübner|Kurt|K|', 'Krebs|Philipp|P|', 'Dobrowolny|Henrik|H|', 'Bielau|Hendrik|H|', 'Steiner|Johann|J|', 'Bogerts|Bernhard|B|']
D000293:Adolescent D000328:Adult D016022:Case-Control Studies D062787:Drug Overdose D005260:Female D005968:Glutamate Decarboxylase D005974:Glutamate-Ammonia Ligase D003932:Heroin D006556:Heroin Dependence D006801:Humans D008297:Male D008875:Middle Aged D009294:Narcotics D019001:Nitric Oxide Synthase D010286:Paraventricular Hypothalamic Nucleus D013702:Temporal Lobe
Neuronal nitric oxide synthase Heroin abuse Immunohistochemistry Morphometry Post-mortem brain