一般口演

一般口演4

2021/9/30　15:00～16:00　オンデマンド D会場 O4-1 単眼の視覚欠如と両眼の視覚欠如が髄鞘形成に与える影響の解析 Oligodendrocytes form normal myelin in the visual pathway when all axons are derived from deprived eyes ^○長内康幸¹, Batpurev Battulga¹, Reiji Yamazaki¹, Mariko Yamamoto², Tom Kouki¹, Megumi Yatabe¹, Hiroaki Mizukami³, Masaki Ueno⁴, Kenta Kobayashi⁵, Yumiko Yoshimura^2,6, Yoshiaki Shinohara¹, Nobuhiko Ohno^1,7 1.Division of Histology and Cell Biology, Department of Anatomy, Jichi Medical University, 2.Division of Visual Information Processing, National Institute for Physiological Sciences, 3.Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, 4.Department of System Pathology for Neurological Disorders, Brain Research Institute, Niigata University, 5.Section of Viral Vector Development, National Institute for Physiological Sciences, 6.Department of Physiological Sciences, The Graduate University for Advanced Studies, 7.Division of Ultrastructural Research, National Institute for Physiological Sciences ^○Yasuyuki Osanai¹, Batpurev Battulga¹, Reiji Yamazaki¹, Mariko Yamamoto², Tom Kouki¹, Megumi Yatabe¹, Hiroaki Mizukami³, Masaki Ueno⁴, Kenta Kobayashi⁵, Yumiko Yoshimura^2,6, Yoshiaki Shinohara¹, Nobuhiko Ohno^1,7 1.Division of Histology and Cell Biology, Department of Anatomy, Jichi Medical University, 2.Division of Visual Information Processing, National Institute for Physiological Sciences, 3.Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, 4.Department of System Pathology for Neurological Disorders, Brain Research Institute, Niigata University, 5.Section of Viral Vector Development, National Institute for Physiological Sciences, 6.Department of Physiological Sciences, The Graduate University for Advanced Studies, 7.Division of Ultrastructural Research, National Institute for Physiological Sciences Experience-dependent myelination is important for cognitive functions, including learning and memory. Recent findings indicate that oligodendrocytes form shorter myelin on axons from the monocularly deprived (MD) mouse eye. However, it remains to be elucidated whether myelin on all axons in the visual pathway would be shorter in the binocularly deprived (BD) mouse. To compare response of chiasmal oligodendrocytes between MD mouse and BD mouse, we simultaneously labeled neuronal axons and oligodendrocytes by viral vectors. We found that myelin length on axons derived from deprived eye was shorter in the MD mouse optic chiasm. Despite both eyes were completely closed, the myelination on the optic chiasm was normal in BD mouse. The myelin thickness of MD mice and BD mice was comparable with that of wild type mice. We conclude that oligodendrocytes form short myelin on deprived axons only when non-deprived axons and deprived axons are intermingled, while oligodendrocytes form normal myelin when all axons are input-deprived axons. We propose that oligodendrocytes myelinate inactive axons normally when no highly active axons are present.		2021/9/30　15:00～16:00　オンデマンド D会場 O4-2 脳梗塞後の壊死組織に出現するミクログリア機能の解析 Role of microglia appearing in the necrotic tissue after cerebral ischemia ^○澤野俊憲¹, Natsumi Yamaguchi¹, Jin Nakatani¹, Shinobu Inagaki^2,3, Takayuki Nakagomi^4,5, Tomohiro Matsuyama⁵, Hidekazu Tanaka¹ 1.生命科学部生命医科学科薬理学研究室, 2.United Graduate School of Child Development, Osaka University, 3.Department of Physical Therapy, Osaka Yukioka College of Health Science, 4.Institute for Advanced Medical Sciences, Hyogo College of Medicine, 5.Department of Therapeutic Progress in Brain Diseases, Hyogo College of Medicine ^○Toshinori Sawano¹, Natsumi Yamaguchi¹, Jin Nakatani¹, Shinobu Inagaki^2,3, Takayuki Nakagomi^4,5, Tomohiro Matsuyama⁵, Hidekazu Tanaka¹ 1.Pharmacology Laboratory, Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, 2.United Graduate School of Child Development, Osaka University, 3.Department of Physical Therapy, Osaka Yukioka College of Health Science, 4.Institute for Advanced Medical Sciences, Hyogo College of Medicine, 5.Department of Therapeutic Progress in Brain Diseases, Hyogo College of Medicine Cerebral ischemia induces tissue necrosis in the ischemic core. We have shown that ischemia-induced multipotent stem cells (iSCs) are induced in the ischemic core, suggesting that ischemic core is active tissue. In this study, we revealed the function of novel microglia in the ischemic core area. Almost microglia died in the ischemic core on day 1 after middle cerebral artery occlusion (MCAO). However, Iba1 (microglia marker)-positive cells reappeared in the ischemic core on day 3. Parabiotic analysis indicated that reappearing Iba1-positive cells were brain resident microglia, but not blood-derived macrophages. Ischemic core microglia abundantly expressed vascular development-related genes.iSCs are derived from brain pericytes, which are vascular lineage. Thus, we investigated the effect of ischemic core microglia on iSCs development. Pharmacological depletion of ischemic core microglia reduced the number of iSCs derived from ischemic core. These results suggest that novel microglia appearing in the ischemic core contribute to the maintenance of iSCs via expression of vascular development-related factors.

2021/9/30　15:00～16:00　オンデマンド D会場 O4-3 アストロサイトにおける核膜ストレスの分子機構 Molecular mechanism of NE stress response in astrocytes ^○上川泰直, Atsushi Saito, Kazunori Imaizumi Department of Biochemistry, Hiroshima University ^○Yasunao Kamikawa, Atsushi Saito, Kazunori Imaizumi Department of Biochemistry, Hiroshima University 　The nuclear envelope (NE) consists of two lipid double membranes and a nuclear lamina. Recent studies revealed that degeneration or degraded quality of NE components impairs nucleocytoplasmic transport as well as genome stability (NE stress), leading to the development of various nuclear envelopathies such as laminopathies. In nervous system, rupture of NE is observed in several neurological disorders such as Dystonia1 and Frontotemporal Dementia, indicating that NE stress plays crucial roles in their pathogenesis. Thus, understanding the mechanisms that regulate proteostasis of the NE at the molecular level is necessary to elucidate the pathology of these diseases and develop the therapeutic strategies. 　Recently, we found that an endoplasmic reticulum membrane resident transcription factor Old Astrocyte Specifically Induced Substance (OASIS) accumulates at the damaged NE. This phenomenon is observed in glioma cells as well as several non-neuronal cells. Some components of the inner nuclear membrane and DNA binding factors also accumulate at the damaged NE together with OASIS. It is well known that exposure to NE stress causes DNA damage. In OASIS KO astrocytes, DNA damage is significantly enhanced after NE stress compared to wild type astrocytes. Collectively, these results suggest that OASIS and its cooperating factors accumulated at the injured NE could protect against NE damage and play crucial roles in NE stress response in astrocytes.		2021/9/30　15:00～16:00　オンデマンド D会場 O4-4 損傷脳内の反応性アストロサイトにおけるErkシグナルの神経保護作用 Neuroprotective role of Erk signaling in reactive astrocytes in the injured brain ^○遠藤光晴, Yuki Tanaka, Hayata Suzuki, Yasuhiro Minami 神戸大学大学院医学研究科細胞生理学分野 ^○Mitsuharu Endo, Yuki Tanaka, Hayata Suzuki, Yasuhiro Minami Division of Cell Physiology, Department of Physiology and Cell Biology, Graduate School of Medicine, Kobe University In the brains under pathological conditions, astrocytes transform into reactive astrocytes in response to inflammation and exert various functions in a context dependent manner. It has become evident that reactive astrocytes play important roles in tissue repair in the injured brain. Recent findings revealed that reactive astrocytes can be classified into at least two different subtypes or states, termed A1 and A2, according to their transcriptomic profiles. However, the molecular mechanism regulating distinct gene expression patterns of reactive astrocytes is largely unknown. In this study, we aimed to elucidate how reactive astrocytes can express A2 astrocyte-specific genes (A2 genes) more prominently and persistently than A1 astrocyte-specific genes (A1 genes) in the injured brains. We found that several types of growth factors, including bFGF, as well as inflammatory cytokines are produced in mouse brain after stab wound injury, and that growth factor signaling enhances inflammatory cytokine-induced expression levels of A2 genes through the activation of Erk signaling. Gene ontology analysis revealed that Erk signaling might confer neuroprotective and angiogenic properties in reactive astrocytes. Erk signaling is indeed activated highly in the reactive astrocytes surrounding immune cells accumulating injury sites for at least two weeks following injury. We will discuss the roles of Erk-activated reactive astrocytes in the injured brain.