Exploring the novel role of mitochondrial dynamics in schizophrenia

在这个项目中，我们希望解决线粒体生物发生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精神分裂症（SZ）的高级脑功能和病理生理。在此，我们报告了项目第四年的新发现如下：我们在人类少突胶质细胞细胞系中发现了pgc -1 α的新变体，这是一种转录辅激活因子，是线粒体生物发生的关键调节因子，并参与了少突胶质细胞的分化。这种变异在人脑中表达。我们使用人类大脑样本进行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）。）该变异的表达与2种参与细胞分化的转录受体相关。现在我们正在用老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原代培养体系，证实在小鼠少突胶质细胞前体细胞分化过程中，新变异的表达增加。

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.