Exploring the novel role of mitochondrial dynamics in schizophrenia

探索线粒体动力学在精神分裂症中的新作用

• 批准号: 19K08041
• 负责人: 岩田 圭子
• 金额: $ 2.83万
• 依托单位: Wakayama Medical University (2022)University of Fukui (2019-2021)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2019
• 资助国家: 日本
• 起止时间: 2019-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-19K08041/
• 关键词: oligodendrocyte; mitochondria; schizophrenia; oligodendrocye

In this project, we wish to address the impact of changes in mitochondrial biogenesis on central nervous system (CNS) development (especially oligodendrocyte differentiation) and animal behavior. Neurons and synapses have long been the dominant focus of neuroscience, informing theories on the pathophysiology of psychiatric disorders. However, the majority of cells in the brain are not neurons but glial cells. We are performing experiments to address how oligodendrocyte differentiation regulated by mitochondria impacts the higher brain functions and pathophysiology of schizophrenia (SZ) following our research methodology and approach.Here, we report new findings by the 4th year of the project as follows;We identified the novel variant of PGC-1alpha, a transcriptional coactivator, which is a key regulator of mitochondrial biogenesis and was involved in oligodendrocyte differentiation using the human oligodendrocyte cell line. The variant was expressed in the human brain. We performed RNA sequences using human brain samples. (The study was Fukui University Medical Research Ethics Committee (approval no.2020028).) The expression of the variant was correlated with 2 transcriptional receptors which were involved in cell differentiation. Now we are conducting in vivo and in vitro experiments using mice. We established the primary culture system of oligodendrocytes at Wakayama Medical Univ and confirmed that the expression of the novel variant was increased during the differentiation of the mouse oligodendrocyte precursor cells.

在这个项目中，我们希望解决线粒体生物发生的变化对中枢神经系统（CNS）发育（特别是少突胶质细胞分化）和动物行为的影响。神经元和突触长期以来一直是神经科学的主要焦点，为精神疾病的病理生理学理论提供了信息。然而，大脑中的大多数细胞不是神经元，而是神经胶质细胞。我们正在按照我们的研究方法和方法进行实验，以解决线粒体调节的少突胶质细胞分化如何影响高级大脑功能和精神分裂症（SZ）的病理生理学。在这里，我们报告了该项目第四年的新发现如下：我们鉴定了 PGC-1alpha 的新变体，它是一种转录共激活因子，是线粒体的关键调节因子。 生物发生并参与使用人少突胶质细胞系的少突胶质细胞分化。该变体在人脑中表达。我们使用人脑样本进行了 RNA 测序。 （该研究由福井大学医学研究伦理委员会批准（批准号：2020028）。）该变异体的表达与参与细胞分化的2个转录受体相关。现在我们正在利用小鼠进行体内和体外实验。我们在和歌山医科大学建立了少突胶质细胞的原代培养系统，并证实了新变体的表达在小鼠少突胶质细胞前体细胞的分化过程中增加。

项目成果

Exploring the novelrole of mitochondrialdynamics inschizophrenia.

探索线粒体动力学在精神分裂症中的新角色。

• 发表时间: 2019
• 作者: Iwata K;Matsuzaki H;Scorrano L
• 通讯作者: Scorrano L

University of Graz(オーストリア)

格拉茨大学（奥地利）

Exploring the novel role of mitochondria dynamics in neuron and oligodendrocyte differentiation

探索线粒体动力学在神经元和少突胶质细胞分化中的新作用

• 发表时间: 2022
• 作者: Mariko Shindo;Takahiro Tsuji;Rahadian Yudo Hartantyo;Ataka Ito;Daisuke Kato;Takayoshi Suganami;Hiroaki Wake;Keiko Iwata et al.
• 通讯作者: Keiko Iwata et al.

Veneto Institute of Molecular Medicine/University of Padova(イタリア)

威尼托分子医学研究所/帕多瓦大学（意大利）

University of Padua/VIMM(イタリア)

帕多瓦大学/VIMM（意大利）