title: The NADPH oxidase NOX2 as a novel biomarker for suicidality: evidence from human post mortem brain samples.
abstract: Recent evidence points towards a role of oxidative stress in suicidality. However, few studies were carried out on the sources of reactive oxygen species (ROS) in subjects with suicidal behaviour. We have previously demonstrated that the NADPH oxidase NOX2-derived oxidative stress has a major role in the development of neuropathological alterations observed in an animal model of psychosis. Here, we investigated the possible increase in NOX2 in post mortem brain samples of subjects who died by asphyctic suicide (AS) compared with controls (CTRL) and subjects who died by non-suicidal asphyxia (NSA). We found that NOX2 expression was significantly higher in the cortex of AS subjects than in the other two experimental groups. NOX2 immunostaining was mainly detected in GABAergic neurons, with a minor presence of NOX2-positive-stained cells in glutamatergic and dopaminergic neurons, as well as astrocytes and microglia. A sustained increase in the expression of 8-hydroxy-2'-deoxyguanosine, an indirect marker of oxidative stress, was also detected in the cortex of AS subjects, compared with CTRL and NSA subjects. A significant elevation in cortical interleukin-6 immunoreactivity in AS subjects suggested an involvement of cytokine-associated molecular pathways in NOX2 elevations. Our results suggest that the increase in NOX2-derived oxidative stress in the brain might be involved in the neuropathological pathways leading to suicidal behaviour. These results may open innovative insights in the identification of new pathogenetic and necroscopic biomarkers, predictive for suicidality and potentially useful for suicide prevention.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Schiavone
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Neri
authors.affiliation: Department of Physiology and Pharmacology, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Mhillaj
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Morgese
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Cantatore
authors.affiliation: Department of Physiology and Pharmacology, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bove
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Riezzo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Tucci
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Pomara
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Turillazzi
authors.affiliation: Department of Physiology and Pharmacology, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Cuomo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Trabace
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001237:Asphyxia / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism; D001344:Autopsy; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D059290:Dopaminergic Neurons / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism; D008875:Middle Aged; D000074662:NADPH Oxidase 2 / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D013405:Suicide; D055815:Young Adult
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D018698:Glutamic Acid; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2