一般口演

一般口演オリゴデンドロサイト

7月7日（金）　10:40-11:40　Room D 2O③-1 不安関連遺伝子産物オリゴデンドロサイト分化を制御する Anxiety-related gene product Rnd2 mediates oligodendrocyte differentiation 深津　翔矢¹, 白井　玲美奈¹, 加藤　裕教², 山内　淳司¹ 1. 東京薬科大学　分子神経科学研究室, 2. 京都大学　大学院生命科学研究科 Shoya Fukatsu¹, Remina Shirai¹, Hironori Katoh², Junji Yamauchi¹ 1. Laboratory of Molecular Neurology, Tokyo University of Pharmacy and Life Sciences, 2. Graduate School of Pharmaceutical Sciences, Kyoto University Oligodendrocyte precursor cells as a central nervous system glial cells differentiate into oligodendrocytes, which wrap their cell membrane around neuronal axons to form the myelin sheath. In spite of myelin sheath formation is a very important cellular morphological change, less is known about the details of the signal pathways. Rnd2, a low GTP-binding protein of the Rho family and anxiety-related gene product, is specifically expressed in neurons of the brain. Although Rnd2 has been reported to be one of the regulators of myelin sheath formation in oligodendrocytes in mice, the molecular mechanisms involved in its differentiation are still unknown. In the present study, we describe the elucidation of a novel differentiation mechanism centered on Rnd2 and its downstream molecules in the FBD-102b cell line, which is the oligodendrocyte model. In the FBD-102b cells, knockdown of Rnd2, Pragmin (a protein downstream of Rnd2), and Fyn (exists in the plasma membrane like Rnd2) significantly inhibited oligodendrocyte precursor cell differentiation. These results indicate that Rnd2 and its surrounding proteins relevance to a signaling pathway involved in oligodendrocyte differentiation.		7月7日（金）　10:40-11:40　Room D 2O③-2 エキソサイトーシスを制御するシグナル複合体のノックダウンでオリゴデンドロサイト分化が抑制される Oligodendrocyte differentiation involves signaling molecules underlying an exocytotic mechanism 宮田　若奈, 白井　玲美奈, 山内　淳司東京薬科大学分子神経科学研究室 Wakana Miyata, Remina Shirai, Junji Yamauchi Laboratory of Molecular Neurology, Tokyo University of Pharmacy and Life Sciences Oligodendroglial cells (oligodendrocytes) migrate and differentiate before wrapping neuronal axons with their differentiated myelin sheaths. Myelin is required not only for achieving efficient electrical transmission but also for protecting neurons. Despite the functional significance of oligodendrocytes, little is known about the molecular mechanism whereby oligodendrocytes differentiate before myelination. Herein we for the first time describe that exocytosis can play a key role in oligodendrocyte differentiation. Knockdown of Exoc5, a key component protein of the intracellular exocyst complex essential for exocytosis, inhibits differentiation in mouse FBD-102b cell line, which is often used for the model line of oligodendrocyte differentiation. These phenomena were accomplished with the results of decreased differentiation marker proteins such as Proteolipid protein 1 (PLP1). Similar observation was obtained in the case of knockdown of Exoc4, the cognate key component to Exoc5. These results suggest that knockdown of the major exocyst subunits inhibits differentiation, potentially presenting their key role of in differentiation at the in vitro level at least.

7月7日（金）　10:40-11:40　Room D 2O③-3 Involvement of mitochondria dynamics in oligodendrocyte differentiation 岩田　圭子¹, 松崎　秀夫², 野口　雅史¹, 新谷　紀人¹ 1. 和歌山県立医大・薬・薬品作用, 2. 福井大・子どもセ・脳機能発達 Keiko Iwata¹, Hideo Matsuzaki², Masahumi Moguchi¹, Norihito Shintani¹ 1. Lab. Pharmacol., Sch. Pharmaceut. Sci., Wakayama Med. Univ., 2. RCCMD, Fukui Univ Emerging evidence indicates that cell fate is pleiotropically regulated by mitochondria, which undergo specific dynamics in the cells. In this study, we explored the possible roles of the mitochondrial dynamics (mtDYN) in neuronal and glial differentiation using in vitro models (SH-SY and MO3.13 cells having the potential to differentiate into neurons and oligodendrocytes (OL), respectively). First, the transcriptome analysis on the mtDYN-related genes was performed, and a common and marked increase was highlighted in the expression levels of PGC-1 alpha in both differentiation models. The differentiation-related increase of PGC-1 alpha, a key regulator of mitochondrial biogenesis, was also confirmed by an immunoblot study during OL differentiation, and interestingly, mRNA analysis suggested the protein was produced from a novel transcript variant, named OL-PGC-1 alpha. Further analyses in the OL differentiation model revealed that specific knockdown of OL-PGC-1 alpha resulted in a significant decrease in the expression of OL differentiation marker proteins. Collectively, the present data at least indicate that OL-PGC-1 alpha plays promotive roles in OL differentiation and open an avenue to study OL mtDYN in the pathophysiology underlying brain dysfunction.		7月7日（金）　10:40-11:40　Room D 2O③-4 遺伝性オリゴデンドロサイト変性疾患に関連するPYCR2異常はミトコンドリア動態を抑制する Genetic oligodendrocyte disease-associated mutations of PYCR2 irregulates mitochondrial dynamics 白井　玲美奈, 山内　淳司東京薬科大学　生命科学部　分子神経科学研究室 Remina Shirai, Junji Yamauchi Laboratory of Molecular Neurology, Tokyo University of Pharmacy and Life Sciences Hypomyelinating leukodystrophy 10 (HLD10) is an autosomal recessive disease related to myelin sheaths in the central nervous system (CNS). Nucleotide mutations of the pyrroline-5-carboxylate reductase 2 (PYCR2) gene are associated with HLD10, likely due to PYCR2’s loss-of-function, and PYCR2 is a mitochondrial residential protein. Here, we describe how each of the HLD10-associated missense mutations, R119C and R251C, lead to forming large size mitochondria in the FBD-102b cell line, which is used as an oligodendroglial cell differentiation model. Expression of each of the mutated R119C and R251C proteins in cells increased the fusion abilities in mitochondria and decreased their fission abilities relatively. The respective mutant proteins, but not wild type proteins also decreased the activities of mitochondria. While cells expressing the wild type proteins exhibited differentiated phenotypes with widespread membranes and increased expression levels of differentiation marker proteins following the induction of differentiation, cells harboring each of the mutant proteins did not. Taken together, these results indicate that an HLD10-associated PYCR2 mutation leads to the formation of large mitochondria with decreased activities, inhibiting oligodendroglial cell morphological differentiation (doi: 10.3390/neurolint14040085).