うつ病・自殺のミクログリア仮説と解明のための橋渡し研究

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  • 加藤 隆弘
    九州大学大学院医学研究院精神病態医学分野

書誌事項

タイトル別名
  • Translational Research to Clarifythe Microglia Hypothesis of Depression and Suicide
  • ウツビョウ ・ ジサツ ノ ミクログリア カセツ ト カイメイ ノ タメ ノ ハシワタシ ケンキュウ

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抄録

Depression is one of the major psychiatric disorders and suicidal behavior is the most crucial symptom of depression. However, the underlying biological mechanisms of depression and suicide have not been well clarified. Microglia, immune cells in the CNS, have recently been highlighted to understand the underlying pathophysiology of not only neurological diseases but also psychiatric disorders. Postmortem brain analysis and PET imaging analysis are two major methods to estimate microglial activation in human subjects, and recent studies using the above-methods have suggested over-activation of microglia in the brain of patients with major depressive disorder especially with suicidal ideation. The above methods have merits, however only a limited aspect of microglial activation can be measured. Dynamic analysis using fresh microglia in human brain is an ideal method, however technological and ethical considerations have limited the ability to conduct research using fresh human microglia. Thus, alternative methods using non-brain tissues are warranted. We have been proposing the multidimensional translational research focusing on microglia especially using human bloods. We have developed a technique to create directly induced microglia-like (iMG) cells from fresh human blood monocytes adding GM-CSF and IL-34 for two weeks, instead of brain biopsy and without the iPS technology. Using the iMG cells, dynamic morphological and molecular-level analyses such as phagocytosis and cytokine releases are applicable. We herein introduce the up-to-date findings using the iMG cells in psychiatry. In addition, we have recently measured blood metabolites in patients with depression using metabolome analysis. We have revealed that tryptophan-kynurenine pathway metabolites, which are known to play important roles in microglia, are significantly corelated to severity of depression and suicidal ideation. We believe that brain analysis and these indirect methods using human bloods shed new light on clarifying dynamic and molecular pathophysiology of microglia in depression, suicide and other psychiatric disorders.

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