Analysis of glial-neuronal network abnormalities in treatment-resistant schizophrenia

2018 Fiscal Year Final Research Report

• Project/Area Number: 15H04894
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Shimane University
• Principal Investigator: Miyaoka Tsuyoshi 島根大学, 学術研究院医学・看護学系, 准教授 (50284047)
• Co-Investigator(Kenkyū-buntansha): 橋岡 禎征 島根大学, 学術研究院医学・看護学系, 講師 (00622523) ; 津森 登志子 県立広島大学, 保健福祉学部(三原キャンパス), 教授 (30217377)
• Research Collaborator: TSUCHIE keiko
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 統合失調症 / グリア細胞

Outline of Final Research Achievements

We are investigating the relationship between glial activation and schizophrenia. In this study, we investigated the postmortem expression of glial cells in the hippocampal region of brains of patients with schizophrenia using an immunofluorescence technique. As a result, although difficult in many cases, we successfully detected immunoreactivities for Iba-1 and S100-β in the dentate gyrus in the postmortem brains.
In addition, we compared the sensitivity of the NMDA-antagonist, ketamine to validate the Gunn rat as a schizophrenia model. By inducing ketamine, Gunn rats exhibited acute hyperactivity and PPI deficits which are positive and negative symptoms respectively of schizophrenia.
Despite its limitations, efforts to document immunohistochemical glial expressions in postmortem brains will provide possible in situ information for the various approaches to using animal models for patients with schizophrenia.

Free Research Field

内科学

Academic Significance and Societal Importance of the Research Achievements

これまでの統合失調症の治療薬はドパミン仮説に基づいて開発されたドパミン受容体遮断薬が主流であるが、治療抵抗性統合失調症にグリア－ニューロン回路網の変化が関与していること（神経炎症仮説）をヒト死後脳で解明する試みは他に例がない。本研究により治療抵抗性統合失調症の治療戦略として「神経炎症を鎮静する」物質を探索することの重要性が高まると同時に、我々が提唱する塩酸ミノサイクリン療法が統合失調症の根治治療薬として位置づけられる可能性も高くなり、学術的にも社会的にも意義深い研究であると考えられる。