Suicide and Microglia: Recent Findings and Future Perspectives Based on Human Studies
Suicide and Microglia: Recent Findings and Future Perspectives Based on Human Studies
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DOI：
10.3389/fncel.2019.00031
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发表时间：
2019-01
影响因子：
5.3
通讯作者：
Hisaomi Suzuki;Masahiro Ohgidani;Nobuki Kuwano;F. Chrétien;G. Lorin de la Grandmaison;M. Onaya;I. Tominaga;Daiki Setoyama;D. Kang;M. Mimura;S. Kanba;Takahiro A. Kato
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文献类型：
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作者：
Hisaomi Suzuki;Masahiro Ohgidani;Nobuki Kuwano;F. Chrétien;G. Lorin de la Grandmaison;M. Onaya;I. Tominaga;Daiki Setoyama;D. Kang;M. Mimura;S. Kanba;Takahiro A. Kato
自杀是精神疾病最灾难性的结果之一。生物精神病学的最新进展表明，某些特定的大脑异常与精神疾病的特定症状之间存在正相关关系，而这些疾病的有机基础以前完全未知。小胶质细胞是大脑中的免疫细胞，被认为通过释放炎症介质在脑部炎症中发挥关键作用，并被认为与抑郁症和精神分裂症等各种精神疾病有关。最近，激活的小胶质细胞被认为是通过各种机制，特别是色氨酸-犬尿氨酸途径，可能导致自杀和自杀行为的细胞之一。专注于精神疾病的动物模型研究有着悠久的历史，然而，能够正确表达精神症状的动物模型却有限。特别是，据我们所知，人类自杀行为的动物模型尚未建立。人们认为自杀仅限于人类，因此尽管存在各种伦理和技术限制，人类受试者仍应成为研究目标。从这个角度来看，我们介绍了关注自杀和小胶质细胞的人类生物学研究。我们首先使用自杀受害者死后的大脑进行神经病理学研究。其次，我们展示了基于正电子发射断层扫描 (PET) 成像和外周血生物标志物分析的最新发现，对有自杀意念和/或自杀相关行为的活体受试者进行分析，特别关注色氨酸-犬尿氨酸途径。最后，我们提出了未来的观点和任务，以利用多维分析方法阐明小胶质细胞在自杀中的作用，重点关注有自杀意念、自杀相关行为和自杀受害者的人类受试者。
Suicide is one of the most disastrous outcomes for psychiatric disorders. Recent advances in biological psychiatry have suggested a positive relationship between some specific brain abnormalities and specific symptoms in psychiatric disorders whose organic bases were previously completely unknown. Microglia, immune cells in the brain, are regarded to play crucial roles in brain inflammation by releasing inflammatory mediators and are suggested to contribute to various psychiatric disorders such as depression and schizophrenia. Recently, activated microglia have been suggested to be one of the possible contributing cells to suicide and suicidal behaviors via various mechanisms especially including the tryptophan-kynurenine pathway. Animal model research focusing on psychiatric disorders has a long history, however, there are only limited animal models that can properly express psychiatric symptoms. In particular, to our knowledge, animal models of human suicidal behaviors have not been established. Suicide is believed to be limited to humans, therefore human subjects should be the targets of research despite various ethical and technical limitations. From this perspective, we introduce human biological studies focusing on suicide and microglia. We first present neuropathological studies using the human postmortem brain of suicide victims. Second, we show recent findings based on positron emission tomography (PET) imaging and peripheral blood biomarker analysis on living subjects with suicidal ideation and/or suicide-related behaviors especially focusing on the tryptophan-kynurenine pathway. Finally, we propose future perspectives and tasks to clarify the role of microglia in suicide using multi-dimensional analytical methods focusing on human subjects with suicidal ideation, suicide-related behaviors and suicide victims.