神経化学
若手育成セミナー出身者によるシンポジウム
若手研究者とシニア研究者で語る日本のオリゴデンドロサイト研究 |
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| 7月8日（土） 16:00-18:00 Room G
3SY⑩-1
オリゴデンドロサイト研究の歴史 ー過去・現在・そして未来ー
History of Oligodendrocyte Research ~Past, Present, and Future~
馬場 広子
新潟医療福祉大学
Hiroko Baba
Niigata University of Health and Welfare
It has been over 100 years since Pio del Rio-Hortega discovered oligodendrocytes and microglia by histological staining using silver carbonate. He also suggested oligodendroglia as myelin-forming cells in the CNS. Since then, researchers have been fascinated by oligodendrocytes/myelin in various aspects. Oligodendrocytes produce tremendous amounts of myelin membrane during active myelination and generate up to 80 myelin sheaths around various axons to promote saltatory conduction. Abnormalities of CNS myelin cause devastating human diseases, multiple sclerosis and leukodystrophies, and relation of oligodendrocyte disfunction to psychiatric disorders has been suggested. Therefore, molecular mechanisms and regulation of oligodendrocyte differentiation and myelination have been studied extensively to understand their roles in normal CNS development as well as in pathological conditions. Recent studies also demonstrated additional roles of oligodendrocytes and its lineage cells in CNS development, function and maintenance, including influence on axonal growth, axonal metabolic support, and activity-dependent myelination. In this talk, history of oligodendrocyte/myelin research in relation to present research direction and future hopes will be discussed. | | 7月8日（土） 16:00-18:00 Room G
3SY⑩-2
Regulations of oligodendrocyte differentiation and myelination by protein-arginine methyltransferases
石野 雄吾, 清水 尚子, 遠山 正彌, 宮田 信吾
近畿大学
Yugo Ishino, Shoko Shimizu, Masaya Tohoyama, Shingo Miyata
Kindai University
Glial cells are recognized as essential components with numerous key roles within the nervous system. Among them, oligodendrocytes and Schwann cells have strong interactions with axons by wrapping them to form myelin sheath in the central nervous system and peripheral nervous system, respectively. Myelin provides support and insulation to the nervous system and is prerequisite for the smooth and high-speed nerve conduction. Therefore, defects and malfunctions of those glial cells have broad impacts within the nervous system. While structural alterations of myelin forming oligodendrocytes in several pathological situation have been illustrated, molecular aspects that account for those defective events remain to be fully understood. A large amount of data has been accumulated about molecular networks which regulate the characteristics of oligodendrocytes throughout their life. In many cases, protein functions are finely controlled by post-translational modifications, such as phosphorylation, methylation, ubiquitylation, sumoylation, glycosylation, and so on. We are now focusing on protein arginine methylations mediated by protein arginine-methyltransferases (PRMTs) for the differentiation of oligodendrocyte and the maintenance of myelin. In this talk, we demonstrate that CARM1, one of PRMTs, is expressed and functioning at the early stage of oligodendrocyte differentiation. | | 7月8日（土） 16:00-18:00 Room G
3SY⑩-3
RNA代謝因子Ddx20によるオリゴデンドロサイトの発生、分化、および恒常性維持機構の解明
Elucidation of the mechanisms underlying Ddx20-mediated regulation of oligodendrocyte development and homeostasis
備前 典久
新潟大学 大学院医歯学総合研究科 脳機能形態学分野
Norihisa Bizen
Div. of Neurobiol. and Anat., Grad. Sch. of Med. and Dent. Sci., Niigata Univ., Niigata, Japan
Oligodendrocytes (OLs) form the myelin sheaths around axons and regulate the axonal conduction and metabolism in the central nervous system (CNS). However, the mechanisms underlying oligodendrocyte development, differentiation, and maturation remain unclear. We identified an RNA helicase Ddx20 (DEAD box protein 20) that binds to Olig2, a bHLH transcription factor essential for OL development. Ddx20 is a multifunctional factor that regulates transcription, RNA metabolism, and translation. We have found that Ddx20 is indispensable for the survival of neural progenitors and OL progenitors (Bizen et al., Cell Death Differ, 2022) and that Ddx20 contributes to OL maturation and the maintenance of myelin-related gene expression (Simankova et al., Glia, 2021). Furthermore, Ddx20 deficiency in OLs led to drastic activation of the p53 pathway in neurons but not OLs, resulting in neuronal loss and axonal degeneration. Interestingly, no activation of the p53 pathway in neurons was observed in the brains of mice with hypomyelination caused by a point mutation in the Plp gene (Jimpy), indicating the dysfunction of Ddx20-deficient OLs, independent of myelin formation, affects neuronal development and survival. These findings suggest that Ddx20 is essential for each stage of OL development, differentiation, and homeostasis. | | 7月8日（土） 16:00-18:00 Room G
3SY⑩-4
脳発達期の免疫システムによるオリゴデンドロサイトの形成と障害機構
Pathophysiology of oligodendrocyte development regulated by immune system in the brain
田辺 章悟, 村松 里衣子
国立精神・神経医療研究センター
Shogo Tanabe, Rieko Muramatsu
Dept. of Mol. Pharmacol., Natl. Inst. Neurosci., National Center of Neurology and Psychiatry
Oligodendrocytes form myelin sheaths that insulate axons in the central nervous system (CNS), which support rapid neurotransmission and the supply of nutrients to neurons. In neurodevelopmental disorders such as autism spectrum disorders (ASD), the impairment of oligodendrocyte development and hypomyelination were observed in several human reports. Thus, understanding the pathophysiological mechanism of oligodendrocyte development is a crucial issue to elucidate the pathological mechanism of neurodevelopmental disorders.
Oligodendrocyte development is regulated by several extrinsic factors including immune cells such as peripheral lymphocytes and microglia. Both peripheral lymphocytes, located in CNS-interface such as meningeal space, choroid plexus and perivascular space, and microglia play crucial roles in brain homeostasis and development by regulating synapse formation, neurogenesis and gliogenesis. We found that unique B cells in neonatal brain contribute to myelin formation by promoting the proliferation of oligodendrocyte precursor cells. In addition, we demonstrated that deficiency of ASD-related genes in microglia led to the impairment of microglia-mediated oligodendrocyte differentiation. In this symposium, we will discuss our current knowledge of the myelination and oligodendrocyte development mechanism regulated by immune system in the developing brain. | | 7月8日（土） 16:00-18:00 Room G
3SY⑩-5
オリゴデンドロサイトを若返らせてみる
Oligodendrocytic NKCC1 activity restores plasticity in the adult mouse brain
阿部 欣史
慶應義塾大学医学部 先端医科学研究所 脳科学研究部門
Yoshifumi Abe
Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan
Various types of plasticity are inducible in the juvenile brain. Myelinated fiber plasticity includes adaptive responses by oligodendrocytes. Oligodendrocytes facilitate the axonal conduction through their physiological level of depolarization. However, the age-dependent properties of oligodendrocyte-related plasticity and its underlying mechanism are largely unknown. Here we show Na+-K+-Cl- co-transporter 1 (NKCC1), which is highly expressed in the juvenile brain, determines the age-dependent facilitation of neural function. The magnitude of axonal plastic changes by optogenetic oligodendrocyte depolarization was larger in juvenile mice than in adult mice, being larger changes sensitive to NKCC1 inhibitor. The reduced plasticity in adults was restored by Nkcc1 overexpression on oligodendrocytes. Moreover, in adult mice with Nkcc1 overexpression, the induction of long-term potentiation and learning were facilitated compared to age-matched control. These findings demonstrate that NKCC1 activity accounts for age-dependent oligodendrocyte-related myelinated fibre plasticity, and that artificial NKCC1 functional activation rejuvenates neural function in the adult brain. | | | |
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