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公募シンポジウム グリアデコーディングにより明かされる脳機能と病態 7月6日（木）　9:00-11:00　Room F 1SY②-1 先端イメージングによるグリア・神経回路の機能解析 New imaging approach toward understanding glia-neural circuit interactions 岡部　繁男 東京大学　大学院医学系研究科　神経細胞生物学 Shigeo Okabe Dept. of Cell Neurobiol., Univ. of Tokyo, Tokyo, Japan Recent findings in glial cell functions in vivo clarified the dominant roles of glial cells in neural circuit development. Dynamic interaction between glial cells and neurons plays an essential role in the activity-dependent refinement of synaptic connections and remodeling of neural circuits in response to sensory inputs. In vivo analyses of glia-neuron interactions require developing new imaging techniques to capture the morphology and function of glial cells and their interaction with neurons in physiological and pathological states. Our laboratory develops several new imaging methods integrated with other modalities. First, long-term in vivo two-photon imaging from deep brain tissue with minimal invasion has enabled imaging of homeostatic clearance of dying neurons by microglia in the hippocampal dentate gyrus. Second, quantitative analysis of neuronal and glial nanostructures by expansion microscopy provides new information about circuit-level alterations in mouse models of neuronal disorders. Finally, an integrated cell transplantation method and high-resolution dendritic spine imaging offer a unique analytical platform for astrocyte-synapse interaction. These multiple techniques are expected to accelerate discoveries about glial involvement in the pathogenesis of brain diseases. 7月6日（木）　9:00-11:00　Room F 1SY②-2 エクソソームによる臓器連関：病態寄与機構と診断マーカーの解析 Inter-organ communication by exosomes: roles in disease etiology and biomarker potential 星野　アユコ 東京大学　先端技術研究センター Ayuko Hoshino RCAST, Univ. of Tokyo, Tokyo, Japan Exosomes, first thought to function only as cellular garbage disposal, are secreted by all cells and have been discovered to function as a cell-cell communication tool. We have previously reported that tumor-derived exosomes localize at their future metastatic sites preparing the pre-metastatic niche. Proteomic profiling of exosomes revealed integrin patterns associated with lung and liver metastasis, whereas CEMIP in brain tropic exosomes enhanced metastasis in the brain. We have also shown that machine learning classification of plasma-derived exosome proteomes revealed high accuracy in identifying cancer as well as in classifying tumor types. More recently, we have expanded our understanding of inter-organ communication by exosome in etiology of preeclampsia (PE). PE, characterized by hypertension and diverse organ damage in the maternal body, is the leading cause of perinatal mortality in the world. Functional analysis using isolated placenta-derived exosomes from normal and PE pregnant women administered to pregnant mice, showed significant increase in proteinuria levels effecting kidney pathology. In this presentation, I will discuss how exosomes define the metastatic sites, potential of exosomes as a disease detection tool and how other type of disease could also be influenced by exchange of exosomes between the organs. 7月6日（木）　9:00-11:00　Room F 1SY②-3 肝臓における新規神経関連マクロファージの同定とその機能解析 Identification of a novel neuron-associated macrophage subset in the liver. Yu Miyamoto, Masaru Ishii 大阪大学大学院医学系研究科免疫細胞生物学 Yu Miyamoto, Masaru Ishii Department of Immunology and Cell Biology, Osaka University, Osaka, Japan Neuron-associated macrophages, shortly NAMs, are one of macrophage subsets which exists on neurons. NAMs have been identified in various peripheral organs including the intestine, skin, lung and adipose tissues. NAMs are responsible for maintaining the tissue integrity through protecting neurons and regulating the immune system. We also newly found out a NAM in the liver, especially on the portal vein. The portal vein is the most pivotal feeding vessel which transports food-derived nutrients from the gastrointestinal tract to the liver. Periportal NAMs (pNAMs) may be responsible for maintaining this vascular homeostasis and controlling the nutrient supply, however, the physiological functions remain uncovered. To reveal detailed molecular expressions of pNAMs, we performed single-cell RNA sequencing and succeeded in identifying the pNAM cluster and its marker molecules. Estimation of physiological functions indicated a possibility that pNAMs sense intravascular substances. To directly demonstrate this function, we established an intravital multiphoton imaging system for the portal vein. As the result, we successfully visualized uptake of intravascular substances by pNAMs. We are currently investigating what happens in neurons after pNAMs sense intravascular substances. Our final goal is to elucidate the importance of pNAM-neuron interactions in liver and portal vein function. 7月6日（木）　9:00-11:00　Room F 1SY②-4 神経活動依存的髄鞘化とその分子メカニズム Activity dependent myelination and the molecular mechanism 和氣　弘明1,2 1. 名古屋大学　大学院医学系研究科　分子細胞学, 2. 自然科学研究機構　生理学研究所　多細胞回路動態研究部門 Hiroaki WAKE1,2 1. Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, 2. Division of Multicellular Circuit Dynamics, National Institute for Physiological Sciences, National Institute of Natural Sciences Oligodendrocyte (OC) forms myelin approximately in around 10 different axons to regulate conduction velocity. Myelin formation in the central nervous system is required for the rapid and the coordinated action potential (AP) propagation across distinct brain regions including cortical and subcortical gray matter, which is important for the information processing. In contrast with the Schwan cell that only form myelin around single axon in peripheral nerve, OC forms myelin around 10 different axons. However, the functional significance for OC to form myelin around different axons remains unknown. In this study, we focused on thalamo-cortical projection and show how activity dependent myelination can affect on motor learning efficacy. In addition, we focus on lipids which is one of the major components of myelin to see their effect on neuronal activity patter and ultimately on behavior output. 7月6日（木）　9:00-11:00　Room F 1SY②-5 アレキサンダー病のミクログリアデコーディング Decoding by microglia of Alexander diseases 小泉　修一1,2 1. 山梨大　院医　薬理, 2. 山梨大　院医　GLIAセンター Schuichi Koizumi1,2 1. Dept Neuropharmacol, Interdisc Grad Sch Med, Univ Yamanashi, 2. Yamanashi GLIA Center, Interdisc Grad Sch Med, Univ Yamanashi Alexander disease (AxD) is a primary astrocyte disease caused by GFAP mutations. However, various factors are involved in its pathogenesis and severity. We previously reported that removal of microglia with a colony stimulating factor 1 receptor antagonist exacerbated the disease, indicating that microglia play a protective role against the disease. However, it remains unclear how microglia sense the pathogenesis of AxD astrocytes and how the sensed microglia suppress AxD disease. Here, we report the mechanism by which microglia sense changes in AxD astrocytes and suppress the disease by Ca2+ imaging of AxD microglia, scRNAseq analysis of AxD brain, and in situ ATP imaging of the hippocampus. microglia in the AxD hippocampus exhibit more frequent Ca2+ signaling compared to wild-type microglia. Ca2+ signaling was more frequent in AxD hippocampal microglia than in wild-type microglia. This enhanced Ca2+ signaling was dependent on P2Y12 receptor activation. P2Y12 receptor antagonists also exacerbated AxD pathology. scRNAseq analysis revealed that NTPDase2, an ATPase expressed in astrocytes, was downregulated in the AxD pathology group, and in situ ATP imaging revealed that extracellular ATP was less degraded in AxD brains. Thus, microglia sensed changes in AxD astrocytes as an increase in extracellular ATP at the P2Y12 receptor and protectively regulated AxD pathology.