公募シンポジウム

公募シンポジウム1【グリアの貪食能による脳の生理・病態制御】

2021/9/30　10:00～12:00　ZOOM A会場 S1-1 生理的・病理的脳におけるミクログリアのシナプス・血管への役割 Microglial function for synapses and vessels in physiological and pathological brain ^○和氣弘明名古屋大学大学院医学系研究科分子細胞学 ^○Hiroaki Wake Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine Microglia are the sole immune responding cells in the central nervous system. Their role as neuro-immune cells in the pathogenesis of various neurodegenerative and infectious diseases of the brain have been extensively studied. In addition to the pathological function of microglia, recent developments in molecular probes and optical imaging in vivo have revealed that microglia are highly motile cell in the healthy brain, extending and retracting their process that extend from a largely stationary cell soma. We used in vivo two photon microscopy to reveal their physiological and pathological function on synapse and vessels. We particularly showed the functional consequence of microglial contact on synapse and vessels to indicate their role in neurological or psychiatric brain. In this session, we will show 1. Microglial regulation of blood brain barrier, 2. Microglial role for cross modal plasticity that indicate their pathological role in schizophrenia.		2021/9/30　10:00～12:00　ZOOM A会場 S1-2 成体脳のニューロン新生における死細胞の貪食過程と意義 Role of microglial phagocytosis of dead cells in adult neurogenesis ^○澤田雅人¹^,²,澤本和延¹^,² 1.名古屋市立大学大学院医学研究科脳神経科学研究所神経発達・再生医学分野,2.生理学研究所神経発達・再生機構研究部門 ^○Masato Sawada¹,²,Kazunobu Sawamoto¹,² 1.Department of Developmental and Regenerative Neurobiology, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, 2.Division of Neural Development and Regeneration, National Institute for Physiological Sciences Even in the adult mammalian brain, newborn neurons are continuously added into the mature neuronal circuitry. On the other hand, old neurons are actively eliminated by cell death, suggesting that the cell death and regeneration (turnover) of adult-born neurons underlies the functions of neuronal circuitry in the brain. However, the mechanisms regulating neuronal turnover in the adult brain are not fully understood.Microglia, the professional phagocytes that reside in the central nervous system, contribute to various facets of adult neurogenesis. Recent studies suggest that microglia secrete and receive chemokines to control the proliferation and differentiation of adult neural stem/progenitor cells. Moreover, microglia phagocytose dead progenitor cells and unwanted synapses in the adult neurogenic niche. However, the role of microglial phagocytosis of dead cells in adult neurogenesis remains unknown.Here we focused on the adult mouse olfactory bulb (OB), a primary center for odor processing, which provides an excellent model to study neuronal turnover in the adult brain. We observed that dead neurons expose phosphatidylserine (PS), an eat-me signal for phagocytes in the immune system, and are efficiently phagocytosed by microglia in the adult OB. To study the role of microglial phagocytosis of dead neurons in neuronal turnover in the adult OB, we masked exposed PS using MFG-E8^D89E, a dominant-negative form of the opsonin MFG-E8, and examined its effects on neuronal turnover in the adult OB. In this symposium, we will present our recent data from these experiments and discuss the importance of dead cell removal by microglial phagocytosis in neuronal turnover in the adult brain.

2021/9/30　10:00～12:00　ZOOM A会場 S1-3 ミクログリアとマクロファージの連携による脳内不要物排出メカニズムと認知症病態 Investigation of a possible microglia and macrophage cooperative pathway responsible for the clearance of waste from the mouse brain in dementia ^○田桑弘之量子科学技術研究開発機構量子生命科学研究所 ^○Hiroyuki Takuwa Institute for Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology Fibrillar tau pathologies have been implicated in Alzheimer’s and related neurodegenerative diseases, although the mechanisms by which the deposition of tau causes brain atrophy remain elusive. To better understand the mechanisms behind brain atrophy, in this study we investigated a cellular pathway that may be responsible for the clearance of tau bearing neurons from the brain. For the purpose of optical imaging, neurons, glia cells and macrophages were labeled with fluorescent protein via an adeno-associated viral (AAV) vector, and fibrillar assemblies of misfolded tau in neurons were labeled with tau specific tracer PM-PBB3. In the brains of transgenic mice models of neurodegenerative tau pathologies, we have longitudinally tracked neurons and glia cell with intravital two-photon laser microscopy and mesoscopy. Neurons bearing tau fibrils underwent primary phagocytosis by rod-shaped microglia, followed by the transport of vesicles containing the neuronal fragments to the brain surface through vertical processes of these microglial cells. The microglia eventually release the neuronal fragments into the cerebrospinal fluid. The neuron fragments were then engulfed by macrophages before being released to the bloodstream. This aggressive elimination of viable neurons led to massive brain atrophy in a progressive manner. Our findings indicate a pathway composed of glial cells and macrophages that may be responsible for the clearance of misfolded proteins and the detrimental removal of neurons from the brain.		2021/9/30　10:00～12:00　ZOOM A会場 S1-4 貪食におけるミクログリアとアストロサイトの連携 Interplay of two brain phagocytes, microglia and astrocytes, in health and disease ^○小西博之,木山博資名古屋大学大学院医学系研究科機能組織学 ^○Hiroyuki Konishi, Hiroshi Kiyama Department of Functional Anatomy and Neuroscience, Nagoya University Graduate School of Medicine Live cell components, such as synapses and myelin, are properly pruned by phagocytosis to refine neural networks. Cell debris and toxic protein aggregates are rapidly cleared by phagocytosis to maintain brain environment. Microglia are known as professional phagocytes that undertake all these phagocytic events. Recently, however, astrocytes have also emerged as phagocytes. Almost all the phagocytic targets of microglia are also phagocytosed by astrocytes, raising a question of how phagocytic activity of these two glial cells is coordinated. In this symposium, we address the cooperation of these cells in phagocytic clearance of cell debris. Using a mouse model of microglia-specific ablation or microglial dysfunction, we revealed that astrocytes are the secondary phagocytes which possess phagocytic machinery even under the healthy condition but perform phagocytosis of cell debris when microglia are impaired. Impairment of microglial phagocytosis could occur in the diseased or aged brain, suggesting that this compensatory function of astrocytes may be important for the maintenance or prolongation of a healthy brain condition.