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神经营养因子表观遗传改变与细胞因子信号传导的联合效应:酒精依赖患者情感症状的一种可能探索模型?

Joint Effects of the Epigenetic Alteration of Neurotrophins and Cytokine Signaling: A Possible Exploratory Model of Affective Symptoms in Alcohol-Dependent Patients?

作者信息

Heberlein Annemarie, Schuster Rilana, Kleimann Alexandra, Groh Adrian, Kordon Andreas, Opfermann Birgitt, Lichtinghagen Ralf, Gröschl Michael, Kornhuber Johannes, Bleich Stefan, Frieling Helge, Hillemacher Thomas

机构信息

Department of Psychiatry, Social Psychiatry and Psychotherapy, Medical School Hanover, Carl-Neuberg-Str. 1, 30625 Hannover, Center for Addiction Research (CARe), Germany.

Central Institute of Mental Health, University Mannheim/Heidelberg, Mannheim,Deutschland.

出版信息

Alcohol Alcohol. 2017 May 1;52(3):277-281. doi: 10.1093/alcalc/agw100.

Abstract

AIMS

Neurotrophins have been linked to the symptomatology of alcohol dependence. We aimed to investigate a possible association between the methylation of the promoters of both neurotrophins, the serum levels of the cytokines and core symptoms of alcohol dependence as withdrawal severity and anxiety.

METHODS

In this study we investigated a possible association between alterations in the methylation of the BDNF IV/NGF I gene promoter and the cytokines tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in 55 male alcohol-dependent patients.

RESULTS

Mean methylation of the promoter of the BDNF gene was significantly associated with the TNF-α serum levels and the CIWA-score during withdrawal (P < 0.001). Moreover, mean methylation of the NGF I promoter was significantly associated with the IL-6 serum levels and STAI-I score during withdrawal (P < 0.001).

CONCLUSION

Our results suggest an association between the epigenetic regulation of both neurotrophins, BDNF and NGF, cytokine release and the symptomatology of alcohol dependence. They imply that changes in the methylation of neurotrophins may contribute to the symptomatology of alcohol dependence by affecting relevant downstream signaling cascades.

摘要

目的

神经营养因子与酒精依赖的症状学有关。我们旨在研究两种神经营养因子启动子的甲基化、细胞因子血清水平与酒精依赖的核心症状(如戒断严重程度和焦虑)之间可能存在的关联。

方法

在本研究中,我们调查了55名男性酒精依赖患者中脑源性神经营养因子IV/神经生长因子I基因启动子甲基化改变与细胞因子肿瘤坏死因子α(TNF-α)和白细胞介素-6(IL-6)之间可能存在的关联。

结果

脑源性神经营养因子基因启动子的平均甲基化与戒断期间的TNF-α血清水平和CIWA评分显著相关(P < 0.001)。此外,神经生长因子I启动子的平均甲基化与戒断期间的IL-6血清水平和STAI-I评分显著相关(P < 0.001)。

结论

我们的结果表明脑源性神经营养因子和神经生长因子这两种神经营养因子的表观遗传调控、细胞因子释放与酒精依赖的症状学之间存在关联。这意味着神经营养因子甲基化的变化可能通过影响相关的下游信号级联反应导致酒精依赖的症状。

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