Schiavone S, Neri M, Mhillaj E, Morgese M G, Cantatore S, Bove M, Riezzo I, Tucci P, Pomara C, Turillazzi E, Cuomo V, Trabace L
Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
Department of Physiology and Pharmacology, 'Sapienza' University of Rome, Rome, Italy.
Transl Psychiatry. 2016 May 17;6(5):e813. doi: 10.1038/tp.2016.76.
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.
近期证据表明氧化应激在自杀行为中起作用。然而，针对有自杀行为的个体中活性氧（ROS）来源的研究较少。我们之前已经证明，NADPH氧化酶NOX2衍生的氧化应激在精神病动物模型中观察到的神经病理学改变的发展中起主要作用。在此，我们研究了与对照组（CTRL）和非自杀性窒息死亡（NSA）的个体相比，窒息性自杀（AS）死亡个体的死后脑样本中NOX2是否可能增加。我们发现，AS个体皮质中的NOX2表达明显高于其他两个实验组。NOX2免疫染色主要在GABA能神经元中检测到，在谷氨酸能和多巴胺能神经元以及星形胶质细胞和小胶质细胞中存在少量NOX2阳性染色细胞。与CTRL和NSA个体相比，在AS个体的皮质中还检测到氧化应激间接标志物8-羟基-2'-脱氧鸟苷的表达持续增加。AS个体皮质中白细胞介素-6免疫反应性显著升高，表明细胞因子相关分子途径参与了NOX2升高。我们的结果表明，大脑中NOX2衍生的氧化应激增加可能参与了导致自杀行为的神经病理学途径。这些结果可能为识别新的致病和尸检生物标志物提供创新性见解，这些标志物可预测自杀行为，并可能有助于预防自杀。
