Abe, Yoichiro

写真a

Affiliation

School of Medicine, Department of Pharmacology (Shinanomachi)

Position

Research Associate/Assistant Professor/Instructor

External Links
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Career 【 Display / hide 】

  • 1997.04
    -
    1999.03

    Institute of Basic Medical Sciences, University of Tsukuba, Department of Pharmacology, Research Associate

  • 1999.04
    -
    2007.03

    School of Medicine, Keio University, Department of Pharmacology, Instructor

  • 2007.04
    -
    2009.03

    School of Medicine, Keio University, Department of Pharmacology, Instructor

  • 2009.04
    -
    Present

    School of Medicine, Keio University, Department of Pharmacology, associate professor

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Academic Degrees 【 Display / hide 】

  • 博士（医学）, University of Tsukuba, Coursework

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Research Areas 【 Display / hide 】

  • Life Science / Molecular biology

  • Life Science / Pharmacology

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Research Keywords 【 Display / hide 】

  • aquaporin-4

  • astrocyte

  • neurodegenerative dieseases

  • neuromyelitis optica

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Papers 【 Display / hide 】

  • Cooling-rate dependence of the cryopreservation of aquaporin-overexpressing cells with a non-permeable cryoprotectant

    Matsuo S., Yamazaki K., Yasui M., Abe Y., Uchida T.

    Cryobiology 119 2025.06

    ISSN  00112240

    　View Summary

    Dehydration of intracellular water is an important factor in the cryopreservation of cells, but questions remain as to the appropriate amount and timing of dehydration and the detailed mechanism of the freezing process. Answering these questions will lead to improvements in cryopreservation methods that have remained unchanged for more than half a century and to an increase in the number of cell types that can be cryopreserved. Therefore, we aimed to reveal the time point when cells were dehydrated in their cooling process and how much their viabilities were improved by dehydration. We conducted cryopreservation experiments using cells with enhanced water permeability due to membrane overexpression of the water transport channel protein (AQP4). The AQP4-expressing cells or non-AQP4-expressing cells were cryopreserved under different cooling rates after addition of the membrane-permeable cryoprotectant (CPA) Me2SO, the non-membrane-permeable CPA trehalose, or no CPA. The results showed that no cryopreservation was successful without CPAs, even in the AQP4-expressing cells with increased water permeability. At slow freezing rates below 35 °C/min, viability with Me2SO was maintained with decreasing in the cooling rate, but with trehalose, the viability decreased. At cooling rates above 80 °C/min, the viability of AQP4-expressing cells was significantly higher than that of AQP4-non-expressing cells. These results suggest that dehydration due to the osmotic-pressure difference generated after extracellular freezing is fatal to cells.

  • Loss of aquaporin-4 impairs cerebrospinal fluid solute clearance through cerebrospinal fluid drainage pathways

    Kato D., Kameda H., Kinota N., Fujii T., Xiawei B., Simi Z., Takai Y., Chau S., Miyasaka Y., Mashimo T., Abe Y., Yasui M., Minowa K., Kudo K.

    Scientific Reports 14 ( 1 )  2024.12

    　View Summary

    The aquaporin-4 (AQP4) water channel is essential in neurofluid dynamics. AQP4 loss impairs solute exchange between the cerebrospinal fluid (CSF) and interstitial fluid (ISF). However, whether AQP4 expression affects solute clearance from the CSF space to the extracranial space remains unclear. This study aimed to investigate this using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) following the intrathecal administration of gadolinium-based contrast agents (GBCAs) to AQP4 knockout (KO) rats. AQP4 KO rats showed reduced efflux of intrathecal GBCAs to the extracranial spaces through CSF drainage pathways and increased retention of intrathecal GBCAs in the CSF space compared with the controls. These results suggest that AQP4 loss impairs solute clearance from the CSF space to the extracranial spaces via the CSF drainage pathways. This study revealed a close relationship between AQP4 expression and CSF solute clearance, contributing to a better understanding of the function of AQP4 in neurofluid dynamics.

  • Humanized-Aquaporin-4-Expressing Rat Created by Gene-Editing Technology and Its Use to Clarify the Pathology of Neuromyelitis Optica Spectrum Disorder

    Namatame C., Abe Y., Miyasaka Y., Takai Y., Matsumoto Y., Takahashi T., Mashimo T., Misu T., Fujihara K., Yasui M., Aoki M.

    International Journal of Molecular Sciences 25 ( 15 )  2024.08

    ISSN  16616596

    　View Summary

    Conventional rodent neuromyelitis optica spectrum disorder (NMOSD) models using patient-derived immunoglobulin G (IgG) are potentially affected by the differences between the human and rodent aquaporin-4 (AQP4) extracellular domains (ECDs). We hypothesized that the humanization of AQP4 ECDs would make the rodent model lesions closer to human NMOSD pathology. Humanized-AQP4-expressing (hAQP4) rats were generated using genome-editing technology, and the human AQP4-specific monoclonal antibody (mAb) or six patient-derived IgGs were introduced intraperitoneally into hAQP4 rats and wild-type Lewis (WT) rats after immunization with myelin basic protein and complete Freund’s adjuvant. Human AQP4-specific mAb induced astrocyte loss lesions specifically in hAQP4 rats. The patient-derived IgGs also induced NMOSD-like tissue-destructive lesions with AQP4 loss, demyelination, axonal swelling, complement deposition, and marked neutrophil and macrophage/microglia infiltration in hAQP4 rats; however, the difference in AQP4 loss lesion size and infiltrating cells was not significant between hAQP4 and WT rats. The patient-derived IgGs bound to both human and rat AQP4 M23, suggesting their binding to the shared region of human and rat AQP4 ECDs. Anti-AQP4 titers positively correlated with AQP4 loss lesion size and neutrophil and macrophage/microglia infiltration. Considering that patient-derived IgGs vary in binding sites and affinities and some of them may not bind to rodent AQP4, our hAQP4 rat is expected to reproduce NMOSD-like pathology more accurately than WT rats.

  • A tyrosine-based YXXΦ motif regulates the degradation of aquaporin-4 via both lysosomal and proteasomal pathways and is functionally inhibited by a 10-amino-acid sequence within its C-terminus

    Wang Y., Suzuki R., Fujii A., Ieki K., Goda W., Yasui M., Abe Y.

    FEBS Journal (FEBS Journal)  290 ( 10 ) 2616 - 2635 2023

    ISSN  1742464X

    　View Summary

    Aquaporin-4 (AQP4) is a dominant water channel in the brain and is expressed on astrocytic end-feet, mediating water homeostasis in the brain. AQP4 is a target of an inflammatory autoimmune disease, neuromyelitis optica spectrum disorders (NMOSD), that causes demyelination. An autoantibody recognizing the extracellular domains of AQP4, called NMO-IgG, is critically implicated in the pathogenesis of the disease. Complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) in astrocytes are the primary causes of the disease, preceding demyelination and neuronal damage. Additionally, some cytotoxic effects of binding of NMO-IgG to AQP4, independent of CDC/ADCC, have been proposed. Antibody-induced endocytosis of AQP4 is thought to be involved in CDC/ADCC-independent cytotoxicity induced by the binding of NMO-IgG to AQP4. To clarify the mechanism responsible for antibody-induced endocytosis of AQP4, we investigated the subcellular localization and trafficking of AQP4, focusing on its C-terminal domain, by making a variety of deletion and substitution mutants of mouse AQP4. We found that a tyrosine-based YXXΦ motif in the C-terminal domain of AQP4 plays a critical role in the steady-state subcellular localization/turnover and antibody-induced endocytosis/lysosomal degradation of AQP4. Our results indicate that the YXXΦ motif has to escape the inhibitory effect of the C-terminal 10-amino-acid sequence and be located at an appropriate distance from the plasma membrane to act as a signal for lysosomal degradation of AQP4. In addition to lysosomal degradation, we demonstrated that the YXXΦ motif also functions as a signal to degrade AQP4 using proteasomes under specific conditions.

  • Aquaporin-4 in Neuromyelitis Optica Spectrum Disorders: A Target of Autoimmunity in the Central Nervous System

    Abe Y., Yasui M.

    Biomolecules (Biomolecules)  12 ( 4 )  2022.04

    　View Summary

    Since the discovery of a specific autoantibody in patients with neuromyelitis optica spectrum disorder (NMOSD) in 2004, the water channel aquaporin-4 (AQP4) has attracted attention as a target of autoimmune diseases of the central nervous system. In NMOSD, the autoantibody (NMO-IgG) binds to the extracellular loops of AQP4 as expressed in perivascular astrocytic end-feet and disrupts astrocytes in a complement-dependent manner. NMO-IgG is an excellent marker for distinguishing the disease from other inflammatory demyelinating diseases, such as multiple sclerosis. The unique higher-order structure of AQP4—called orthogonal arrays of particles (OAPs)—as well as its subcellular localization may play a crucial role in the pathogenesis of the disease. Recent studies have also demonstrated complement-independent cytotoxic effects of NMO-IgG. Antibody-induced endocytosis of AQP4 has been suggested to be involved in this mechanism. This review focuses on the binding properties of antibodies that recognize the extracellular region of AQP4 and the characteristics of AQP4 that are implicated in the pathogenesis of NMOSD.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

  • Prolonged Light Exposure Induces Circadian Impairment in Aquaporin-4-Knockout Mice

    Murakami A., Tsuji K., Isoda M., Matsuo M., Abe Y., Yasui M., Okamura H., Tominaga K.

    Journal of Biological Rhythms (Journal of Biological Rhythms)  38 ( 2 ) 208 - 214 2023

    ISSN  07487304

    　View Summary

    Astrocytes are densely present in the suprachiasmatic nucleus (SCN), which is the master circadian oscillator in mammals, and are presumed to play a key role in circadian oscillation. However, specific astrocytic molecules that regulate the circadian clock are not yet well understood. In our study, we found that the water channel aquaporin-4 (AQP4) was abundantly expressed in SCN astrocytes, and we further examined its circadian role using AQP4-knockout mice. There was no prominent difference in circadian behavioral rhythms between Aqp4-/- and Aqp4+/+ mice subjected to light-dark cycles and constant dark conditions. However, exposure to constant light induced a greater decrease in the Aqp4-/- mice rhythmicity. Although the damped rhythm in long-term constant light recovered after transfer to constant dark conditions in both genotypes, the period until the reappearance of original rhythmicity was severely prolonged in Aqp4-/- mice. In conclusion, AQP4 absence exacerbates the prolonged light-induced impairment of circadian oscillations and delays their recovery to normal rhythmicity.

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Presentations 【 Display / hide 】

  • Development of a new Neuromyelitis Optica model mice.

    Chau SH, Abe Y, Yasui M

    The 18th World Congress of Basic and Clinical Pharmacology/The 91st Annual Meeting of the Japanese Pharmacological Society (Kyoto) , 

    2018.07
    , 

    Poster presentation, 日本薬理学会

  • Roles of the C-terminal domain in intracellular trafficking and degradation of AQP4.

    Abe Y, Fujii A, Goda W, and Yasui M

    The 40th Annual Meeting of the Molecular Biology Society of Japan (Kobe) , 

    2017.12
    , 

    Poster presentation

  • Aquaporin-4 is not involved in chronic neuroinflammatory responses in 5xFAD mice.

    Abe Y, Chau S, Wada H, Yasui M, and Niikura T

    The 90th Annual Meeting of the Japanese Pharmacological Society (Nagasaki) , 

    2017.03
    , 

    Poster presentation

  • Glial responses to amyloid β accumulation in aquaporin-4-deficient Alzheimer’s disease model.

    Abe, Y., Chau, S., Wada, H., Yasui, M., and Niikura, T.

    The 39th Annual Meeting of the Japan Neuroscience Society (Yokohama) , 

    2016.07
    , 

    Poster presentation

  • High avidity chimeric monoclonal antibodies against the extracellular domains of human aquaporin-4 competing with NMO-IgG.

    Miyazaki-Komine, K, Abe, Y., Huang, P., Takai, Y., Kusano-Arai, O., Iwanari, H., Misu, T., Sakihama, T., Toyama, Y., Fujihara, K., Hamakubo, T., and Yasui, M.

    The 88th Annual Meeting of the Japanese Pharmacological Society (Nagoya) , 

    2015.03
    , 

    Poster presentation

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • アクアポリン４機能と脳リンパ排泄機構に着目したアルツハイマー病発症機構の解明

    2017.04
    -
    2019.03

    日本学術振興会, Grant-in-Aid for Scientific Research, Research grant, Principal investigator

  • 視神経脊髄炎の動物モデルと抗アクアポリン４抗体を用いた新規治療法の開発基盤研究

    2016.04
    -
    2019.03

    日本学術振興会, Grant-in-Aid for Scientific Research, Research grant, Principal investigator

  • アルツハイマー病モデルマウスを用いたAβ蓄積から神経原繊維変化へ至る機構の解明

    2013.04
    -
    2015.03

    日本学術振興会, Grant-in-Aid for Scientific Research, Research grant, Principal investigator

  • アクアポリン4ノックアウトマウスを用いた新規視神経脊髄炎モデルの作製とその解析

    2010.04
    -
    2013.03

    日本学術振興会, Grant-in-Aid for Scientific Research, Research grant, Principal investigator

  • FALS変異SOD1導入ES細胞由来in vitroモデル神経細胞の樹立と解析

    2004.04
    -
    2006.03

    日本学術振興会, Grant-in-Aid for Scientific Research, Research grant, Principal investigator

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Courses Taught 【 Display / hide 】

  • PHARMACOLOGY

    2025

  • PHARMACOLOGY

    2024

  • PHARMACOLOGY

    2023

  • PHARMACOLOGY

    2022

  • PHARMACOLOGY

    2021

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Courses Previously Taught 【 Display / hide 】

  • 薬理学

    Keio University

    2015.04
    -
    2016.03
    , 

    Spring Semester

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Memberships in Academic Societies 【 Display / hide 】

  • 日本分子生物学会, 

    2011
    -
    Present

  • 日本神経科学学会, 

    2008
    -
    Present

  • Society for Neuroscience, 

    2003
    -
    Present

  • 日本再生医療学会, 

    2002
    -
    2010

  • 日本薬理学会, 

    1993
    -
    Present
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