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.
Highlights
Psychiatric disorders, such as depression, bipolar disorders and psychosis, are associated with high risk of suicide.[1]
In order to investigate whether NOX2-derived oxidative stress might be involved in deaths by suicide, we performed immunohistochemical analysis for NOX2, focusing on the cortex of asphyctic suicide (AS) subjects, compared with CTRL and NAS subjects
Whereas the presence of only few NOX2-positive-stained cells was observed in non-suicidal asphyxia (NSA) subjects, a significant increase in the number of NOX2-immunoreactive cells was detected in AS subjects
Summary
Psychiatric disorders, such as depression, bipolar disorders and psychosis, are associated with high risk of suicide.[1]. Increasing evidence shows a possible contribution of brain oxidative stress and increased reactive oxygen species (ROS) production in the central nervous system (CNS) in the development of suicidal behaviour.[7] Possible sources of ROS include the NADPH oxidase NOX2 enzyme, which is a protein that transfers electrons across biological membranes to produce superoxide This enzyme is constitutively expressed in the CNS and is a major generator of ROS in several pathological conditions, from psychiatric to neurodegenerative diseases.[8] In particular, we recently demonstrated that early NOX2 increase in specific brain areas contributes to the development of neuropathological alterations observed in non-pharmacologic and pharmacologic rodent models of psychosis, such as the social isolation and the ketamine model, respectively.[9,10,11]
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