Involvement of mitochondrial dysfunction in disrupted oscillatory brain activity in relation to cognitive deficits with schizophrenia.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07949
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Wakayama Medical University (2021-2022); Nara Medical University (2020)
• Principal Investigator: KIMOTO SOHEI 和歌山県立医科大学, 医学部, 教授 (00405391)
• Co-Investigator(Kenkyū-buntansha): 橋本 隆紀 金沢大学, 医学系, 協力研究員 (40249959) ; 山室 和彦 奈良県立医科大学, 医学部, 学内講師 (60526721)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 死後脳解析 / 認知機能障害 / 統合失調症 / ミトコンドリア / 酸化的リン酸化 / 樹状突起スパイン / アクチン動態

Outline of Final Research Achievements

Visuospatial working memory(VsWM), which is impaired in schizophrenia, is mediated by a distributed cortical network. VsWM is predominantly mediated by coordinated neural activity across a distributed cortical neural network that includes nodes in primary and association visual regions of the occipital lobes which convey visual information to nodes in the posterior parietal cortex and dorsolateral prefrontal cortex. To understand the biological basis for altered VsWM in schizophrenia, we used posrmortem brain analysis to assess levels of actin- and OXPHOS-related transcripts and TMEM59 expression from the DLPFC and three other cortical regions of the VsWM network between healthy comparisons and schizophrenia subjects. The differential alterations in markers of actin assembly and energy production across regions of the cortical VsWM network in SZ suggest that each region may make specific contributions to VsWM impairments in the illness.

Free Research Field

分子精神医学

Academic Significance and Societal Importance of the Research Achievements

統合失調症の認知機能障害は、日常生活や予後に大きな影響を与えることがわかっている。認知機能障害の生物基盤を明らかにするために、大脳ネットワークレベルで、死後脳を使って検討を行ない、その病態基盤の一助を明らかにした。本研究の成果の発展が、治療薬の創発に繋がると考えている。