Abe, Yoichiro

写真a

Affiliation

School of Medicine, Department of Pharmacology ( Shinanomachi )

Position

Research Associate/Assistant Professor/Instructor

External Links
Scopus Paper Info  
Paper Count: 57 Citation Count: 2728 h-index: 28

Click to view the Scopus page. The data was downloaded from Scopus API in August 23, 2026, via http://api.elsevier.com and http://www.scopus.com .

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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 】

  • LRBA organizes distinct vesicular traffcking systems in distal nephron segments for water and sodium conservation

    Nagaoka K., Ando F., Fujiki T., Abolhassani H., Hara Y., Yanagawa H., Suzuki S., Sakamaki Y., Oikawa D., Kikuchi H., Mandai S., Mori Y., Mori T., Susa K., Sohara E., Hoshino A., Ito T., Arakawa Y., Sasahara Y., Yasuda S., Abe Y., Yasui M., Tokunaga F., Kanegane H., Uchida S.

    Proceedings of the National Academy of Sciences of the United States of America 123 ( 18 )  2026.05

    ISSN  00278424

    　View Summary

    Lipopolysaccharide-responsive and beige-like anchor protein (LRBA) defciency is a rare genetic disorder characterized by immune dysregulation. Te immune checkpoint molecule cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) fails to perform proper membrane trafcking in the absence of LRBA. In addition to immune cells, LRBA localizes to intracellular vesicles in various epithelial cells; however, its physiological roles have not been accurately deciphered. It was observed in this study that LRBA facilitates water and sodium transport by promoting vesicular trafcking of aquaporin-2 (AQP2) and AQP4 in renal collecting duct cells and that of sterile 20/SPS1-related proline/alanine-rich kinase (SPAK) in distal convoluted tubule cells. Consequently, Lrba knockout mice exhibited vasopressin-resistant polyuria and hypotension under sodium-restricted conditions. Tis registry study revealed a polyuric phenotype in a subset of patients with LRBA defciency, characterized by inappropriately low urine specifc gravity despite the presence of chronic diarrhea. Notably, desmopressin treatment ameliorated impaired urinary concentration in a mouse model of human LRBA defciency. LRBA functions as a central coordinator of fuid and sodium homeostasis by organizing segment-specifc vesicular trafcking systems in renal epithelial cells.

  • Early neuromyelitis optica antibody-induced molecular changes in aquaporin 4 and associated proteins at astrocyte endfeet in murine brain tissues

    Yoshikawa Y., Tomioka M., Abe Y., Yasui M., Nuriya M.

    Journal of Pharmacological Sciences 158 ( 3 ) 212 - 218 2025.07

    ISSN  13478613

    　View Summary

    Neuromyelitis optica spectrum disorder (NMOSD) is characterized by the production of autoantibodies against aquaporin 4 (AQP4). Because NMOSD progressively causes irreversible and severe neurological damages, understanding the initial molecular changes induced by anti-AQP4 antibody binding is crucial for designing early interventions. However, knowledge about the effects of the antibodies before AQP4 loss in brain tissues is limited. Using acutely prepared mouse brain slices, we aimed to investigate the initial molecular impact of NMO model antibodies on AQP4 and its associated proteins. We employed two different types of NMO model antibodies, E5415A and E5415B; E5415A recognizes both M1 and M23 isoforms, whereas E5415B exclusively binds to M23. We found that E5415A but not E5415B disrupted the uniform perivascular localization of AQP4, leading to fragmentation. We further addressed the impact of these changes on AQP4-associated proteins and found that strong colocalizations between AQP4 and dystrophin-glycoprotein complex (DGC) components were preserved, even after AQP4 localization pattern became fragmented. Thus, our study reveals the initial molecular changes in the AQP4 channel at the astrocytic endfeet in response to NMO model antibodies and highlights the early pathological events occurring in NMOSD.

  • 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.

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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

    [International presentation]  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

    [Domestic presentation]  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

    [Domestic presentation]  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.

    [Domestic presentation]  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.

    [Domestic presentation]  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

    2026

  • INTRODUCTION TO MEDICINE

    2026

  • MEDICAL SCIENCE METHODOLOGY

    2026

  • COORDINATED CURRICULUM ON BEING A PROFESSIONAL STUDENT IN MEDICAL SCIENCES

    2026

  • PHARMACOLOGY

    2025

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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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