María S. García-Gutiérrez , Esther Caparros , Abraham B. Torregrosa , Sebastián Martínez-López , Ani Gasparyan , Salvador Giner , Jorge Manzanares
{"title":"自杀者前额叶皮层背外侧亲、抗炎细胞因子平衡及超氧化物歧化酶的改变。","authors":"María S. García-Gutiérrez , Esther Caparros , Abraham B. Torregrosa , Sebastián Martínez-López , Ani Gasparyan , Salvador Giner , Jorge Manzanares","doi":"10.1016/j.neurot.2025.e00634","DOIUrl":null,"url":null,"abstract":"<div><div>Recent studies have suggested that the immune system may be a key player in the pathophysiology of suicide. In this context, access to brain samples from individuals who died by suicide is of particular importance. Our study is designed to thoroughly investigate the link between suicide and brain immune system alterations. We analyzed changes in gene and protein expression of proinflammatory cytokines, IL-6 and TGF-β, and anti-inflammatory cytokine, IL-10, in the dorsolateral prefrontal cortex (DLPFC) of 33 suicide decedents (S) (with no clinical psychiatric history or treatment with anxiolytics or antidepressants) and 29 controls (C) using qPCR and ELISAs, respectively. Additionally, we evaluated superoxide dismutase 1 (SOD1) activity using ELISAs. S and C were matched for age and postmortem interval. Our results revealed an inverse correlation between pro- and anti-inflammatory cytokine levels in the DLPFC of S compared to C, with IL-6 and TGF-β increased and IL-10 reduced. Interestingly, contrasting changes were noted in gene expression across all analyzed targets, suggesting a potential homeostatic compensatory mechanism that warrants further analysis in large-scale studies. These alterations were accompanied by lower SOD1 activity in the DLPFC of S compared to C. These findings indicate an association between an inflammatory brain state and increased oxidative stress with suicide.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 5","pages":"Article e00634"},"PeriodicalIF":6.9000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Alterations of pro- and anti-inflammatory cytokines balance and superoxide dismutase in the dorsolateral prefrontal cortex of suicide decedents\",\"authors\":\"María S. García-Gutiérrez , Esther Caparros , Abraham B. Torregrosa , Sebastián Martínez-López , Ani Gasparyan , Salvador Giner , Jorge Manzanares\",\"doi\":\"10.1016/j.neurot.2025.e00634\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Recent studies have suggested that the immune system may be a key player in the pathophysiology of suicide. In this context, access to brain samples from individuals who died by suicide is of particular importance. Our study is designed to thoroughly investigate the link between suicide and brain immune system alterations. We analyzed changes in gene and protein expression of proinflammatory cytokines, IL-6 and TGF-β, and anti-inflammatory cytokine, IL-10, in the dorsolateral prefrontal cortex (DLPFC) of 33 suicide decedents (S) (with no clinical psychiatric history or treatment with anxiolytics or antidepressants) and 29 controls (C) using qPCR and ELISAs, respectively. Additionally, we evaluated superoxide dismutase 1 (SOD1) activity using ELISAs. S and C were matched for age and postmortem interval. Our results revealed an inverse correlation between pro- and anti-inflammatory cytokine levels in the DLPFC of S compared to C, with IL-6 and TGF-β increased and IL-10 reduced. Interestingly, contrasting changes were noted in gene expression across all analyzed targets, suggesting a potential homeostatic compensatory mechanism that warrants further analysis in large-scale studies. These alterations were accompanied by lower SOD1 activity in the DLPFC of S compared to C. These findings indicate an association between an inflammatory brain state and increased oxidative stress with suicide.</div></div>\",\"PeriodicalId\":19159,\"journal\":{\"name\":\"Neurotherapeutics\",\"volume\":\"22 5\",\"pages\":\"Article e00634\"},\"PeriodicalIF\":6.9000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurotherapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1878747925001126\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurotherapeutics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1878747925001126","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Alterations of pro- and anti-inflammatory cytokines balance and superoxide dismutase in the dorsolateral prefrontal cortex of suicide decedents
Recent studies have suggested that the immune system may be a key player in the pathophysiology of suicide. In this context, access to brain samples from individuals who died by suicide is of particular importance. Our study is designed to thoroughly investigate the link between suicide and brain immune system alterations. We analyzed changes in gene and protein expression of proinflammatory cytokines, IL-6 and TGF-β, and anti-inflammatory cytokine, IL-10, in the dorsolateral prefrontal cortex (DLPFC) of 33 suicide decedents (S) (with no clinical psychiatric history or treatment with anxiolytics or antidepressants) and 29 controls (C) using qPCR and ELISAs, respectively. Additionally, we evaluated superoxide dismutase 1 (SOD1) activity using ELISAs. S and C were matched for age and postmortem interval. Our results revealed an inverse correlation between pro- and anti-inflammatory cytokine levels in the DLPFC of S compared to C, with IL-6 and TGF-β increased and IL-10 reduced. Interestingly, contrasting changes were noted in gene expression across all analyzed targets, suggesting a potential homeostatic compensatory mechanism that warrants further analysis in large-scale studies. These alterations were accompanied by lower SOD1 activity in the DLPFC of S compared to C. These findings indicate an association between an inflammatory brain state and increased oxidative stress with suicide.
期刊介绍:
Neurotherapeutics® is the journal of the American Society for Experimental Neurotherapeutics (ASENT). Each issue provides critical reviews of an important topic relating to the treatment of neurological disorders written by international authorities.
The Journal also publishes original research articles in translational neuroscience including descriptions of cutting edge therapies that cross disciplinary lines and represent important contributions to neurotherapeutics for medical practitioners and other researchers in the field.
Neurotherapeutics ® delivers a multidisciplinary perspective on the frontiers of translational neuroscience, provides perspectives on current research and practice, and covers social and ethical as well as scientific issues.