Microglia in the dorsal raphe nucleus plays a potential role in both suicide facilitation and prevention in affective disorders.
Microglia in the dorsal raphe nucleus plays a potential role in both suicide facilitation and prevention in affective disorders.
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DOI：
10.1007/s00406-017-0774-1
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发表时间：
2017-08
影响因子：
4.7
通讯作者：
Gos T
中科院分区：
文献类型：
--
作者：
Brisch R;Steiner J;Mawrin C;Krzyżanowska M;Jankowski Z;Gos T
在自杀的发病机制中，不断有关于中枢神经系统参与的报道。中缝背核（DRN）是自杀行为中前脑边缘结构受干扰的多巴胺能神经支配的主要来源，其中异常的小胶质细胞反应似乎起了作用。在我们目前的研究中，对DRN中HLA-DR抗原免疫染色的小胶质细胞密度进行了评估。这些分析进行了石蜡包埋的大脑从24自杀和21非自杀患者，其中，27抑郁症（15重性抑郁症和12双相情感障碍）和18精神分裂症（9残留和9偏执）患者和22个匹配的对照无精神障碍。只有非自杀性抑郁亚组显示出显著较低的小胶质细胞反应，即，HLA-DR阳性小胶质细胞的密度与抑郁自杀受害者和对照组相比均降低。这种效应与抗抑郁药或抗精神病药无关，因为前者与非自杀性抑郁症患者的小胶质细胞密度呈正相关，而后者则没有影响。此外，将这些结果与我们先前发表的来自同一队列的研究人员的数据进行比较（Krzyelanowska等人，精神病学研究241：43-46），表明小胶质细胞对非自杀性抑郁亚组中DRN神经元中的核糖体DNA转录有积极影响，但在抑郁自杀病例中没有。因此，小胶质细胞和DRN中的神经元之间的相互作用可能以相反的方式参与抑郁症患者的自杀促进和预防。
An involvement of the central serotonergic system has constantly been reported in the pathogenesis of suicide. The dorsal raphe nucleus (DRN) is the main source of serotonergic innervation of forebrain limbic structures disturbed in suicidal behaviour, in which an abnormal microglia reaction seems to play a role. In our present study, the density of microglia immunostained for the HLA-DR antigen was evaluated in the DRN. These analyses were carried out on paraffin-embedded brains from 24 suicidal and 21 non-suicidal patients; among them, 27 depressed (15 major depressive disorder and 12 bipolar disorder) and 18 schizophrenia (9 residual and 9 paranoid) patients and 22 matched controls without mental disorders. Only the non-suicidal depressed subgroup revealed significantly lower microglial reaction, i.e., a decreased density of HLA-DR positive microglia versus both depressed suicide victims and controls. The effect was not related to antidepressant or antipsychotic medication, as the former correlated positively with microglial density in non-suicidal depressed patients, and the latter had no effect. Moreover, the comparison of these results with previously published data from our workgroup in the same cohort (Krzyżanowska et al. in Psychiatry Res 241:43–46,) suggested a positive impact of microglia on ribosomal DNA transcription in DRN neurons in the non-suicidal depressed subgroup, but not in depressed suicidal cases. Therefore, the interaction between microglia and neurons in the DRN may be potentially involved in opposite ways regarding suicide facilitation and prevention in the tested subgroups of depressed patients.
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