Abe, Yoichiro



School of Medicine, Department of Pharmacology (Shinanomachi)


Research Associate/Assistant Professor/Instructor

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Career 【 Display / hide

  • 1997.04

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

  • 1999.04

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

  • 2007.04

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

  • 2009.04

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

Academic Degrees 【 Display / hide

  • 博士(医学), University of Tsukuba, Coursework


Research Areas 【 Display / hide

  • Molecular biology

  • General pharmacology

Research Keywords 【 Display / hide

  • aquaporin-4

  • astrocyte

  • neurodegenerative dieseases

  • neuromyelitis optica


Papers 【 Display / hide

  • Di-lysine motif-like sequences formed by deleting the C-terminal domain of aquaporin-4 prevent its trafficking to the plasma membrane

    Chau S., Fujii A., Wang Y., Vandebroek A., Goda W., Yasui M., Abe Y.

    Genes to Cells (Genes to Cells)  26 ( 3 ) 152 - 164 2021.03

    ISSN  13569597

     View Summary

    Aquaporin-4 is a transmembrane water channel protein, the C-terminal domain of which is facing the cytosol. In the process of investigating the role of the C-terminal domain of aquaporin-4 with regard to intracellular trafficking, we observed that a derivative of aquaporin-4, in which the C-terminal 53 amino acids had been removed (Δ271-323), was localized to intracellular compartments, including the endoplasmic reticulum, but was not expressed on the plasma membranes. This was determined by immunofluorescence staining and labeling of the cells with monoclonal antibody specifically recognizing the extracellular domain of aquaporin-4, followed by confocal microscopy and flow cytometry. Deletion of additional amino acids in the C-terminal domain of aquaporin-4 led to its redistribution to the plasma membrane. This suggests that the effect of the 53-amino acid deletion on the subcellular localization of aquaporin-4 could be attributed to the formation of a signal at the C terminus that retained aquaporin-4 in intracellular compartments, rather than the loss of a signal required for plasma membrane targeting. Substitution of the lysine at position 268 with alanine could rescue the Δ271-323-associated retention in the cytosol, suggesting that the C-terminal sequence of the mutant served as a signal similar to a di-lysine motif.

  • Behavioral and electrophysiological evidence for a neuroprotective role of aquaporin-4 in the 5xFAD transgenic mice model

    Abe Y., Ikegawa N., Yoshida K., Muramatsu K., Hattori S., Kawai K., Murakami M., Tanaka T., Goda W., Goto M., Yamamoto T., Hashimoto T., Yamada K., Shibata T., Misawa H., Mimura M., Tanaka K.F., Miyakawa T., Iwatsubo T., Hata J.I., Niikura T., Yasui M.

    Acta Neuropathologica Communications (Acta Neuropathologica Communications)  8 ( 1 ) 67 2020.05

    Research paper (scientific journal), Joint Work, Accepted

     View Summary

    © 2020 The Author(s). Aquaporin-4 (AQP4) has been suggested to be involved in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD), which may be due to the modulation of neuroinflammation or the impairment of interstitial fluid bulk flow system in the central nervous system. Here, we show an age-dependent impairment of several behavioral outcomes in 5xFAD AQP4 null mice. Twenty-four-hour video recordings and computational analyses of their movement revealed that the nighttime motion of AQP4-deficient 5xFAD mice was progressively reduced between 20 and 36 weeks of age, with a sharp deterioration occurring between 30 and 32 weeks. This reduction in nighttime motion was accompanied by motor dysfunction and epileptiform neuronal activities, demonstrated by increased abnormal spikes by electroencephalography. In addition, all AQP4-deficient 5xFAD mice exhibited convulsions at least once during the period of the analysis. Interestingly, despite such obvious phenotypes, parenchymal amyloid β (Aβ) deposition, reactive astrocytosis, and activated microgliosis surrounding amyloid plaques were unchanged in the AQP4-deficient 5xFAD mice relative to 5xFAD mice. Taken together, our data indicate that AQP4 deficiency greatly accelerates an age-dependent deterioration of neuronal function in 5xFAD mice associated with epileptiform neuronal activity without significantly altering Aβ deposition or neuroinflammation in this mouse model. We therefore propose that there exists another pathophysiological phase in AD which follows amyloid plaque deposition and neuroinflammation and is sensitive to AQP4 deficiency.

  • Stagnation of glymphatic interstitial fluid flow and delay in waste clearance in the SOD1-G93A mouse model of ALS

    Hirose M., Asano M., Watanabe-Matsumoto S., Yamanaka K., Abe Y., Yasui M., Tokuda E., Furukawa Y., Misawa H.

    Neuroscience Research (Neuroscience Research)   2020

    ISSN  01680102

     View Summary

    Overexpression and mislocalization of aquaporin-4 (AQP4) in the SOD1G93A mouse model of amyotrophic lateral sclerosis (ALS) have previously been reported. However, how alterations of AQP4 affect interstitial bulk flow in the brain and spinal cord, the so-called glymphatic system, is unclear. Here, we report an enhanced accumulation of disease-associated SOD1 species including SOD1 oligomers in SOD1G93A;AQP4−/− mice compared with SOD1G93A mice during ALS disease progression, as analyzed by sandwich ELISA. By directly injecting SOD1 oligomers into the spinal cord parenchyma, we observed a significantly larger delay in clearance of biotinylated or fluorescent-labeled SOD1 oligomers in AQP4−/− mice than in wild-type mice. Furthermore, when we injected the fluorescent-labeled tracer protein ovalbumin into the cisterna magna and analyzed the tracer distribution in the cervical spinal cord, approximately 35 % processing ability was found to be reduced in SOD1G93A mice compared to wild-type mice. These results suggest that the glymphatic system is abnormal and that waste clearance is delayed in SOD1G93A mice.

  • Aquaporin 4 Suppresses Neural Hyperactivity and Synaptic Fatigue and Fine-Tunes Neurotransmission to Regulate Visual Function in the Mouse Retina

    Ozawa Y., Toda E., Kawashima H., Homma K., Osada H., Nagai N., Abe Y., Yasui M., Tsubota K.

    Molecular Neurobiology (Molecular Neurobiology)  56 ( 12 ) 8124 - 8135 2019.12

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  08937648

     View Summary

    © 2019, The Author(s). The bidirectional water channel aquaporin 4 (AQP4) is abundantly expressed in the neural tissue. The advantages and disadvantages of AQP4 neural tissue deficiency under pathological conditions, such as inflammation, and relationship with neural diseases, such as Alzheimer’s disease, have been previously reported. However, the physiological functions of AQP4 are not fully understood. Here, we evaluated the role of AQP4 in the mouse retina using Aqp4 knockout (KO) mice. Aqp4 was expressed in Müller glial cells surrounding the synaptic area between photoreceptors and bipolar cells. Both scotopic and photopic electroretinograms showed hyperactive visual responses in KO mice, gradually progressing with age. Moreover, the amplitude reduction after frequent stimuli and synaptic fatigue was more severe in KO mice. Glutamine synthetase, glutamate aspartate transporter, synaptophysin, and the inward potassium channel Kir2.1, but not Kir4.1, were downregulated in KO retinas. KIR2.1 colocalized with AQP4 in Müller glial cells at the synaptic area, and its expression was affected by Aqp4 levels in primary Müller glial cell cultures. Intraocular injection of potassium in wild-type mice led to visual function hyperactivity, as observed in Aqp4 KO mice. Mitochondria molecules, such as Pgc1α and CoxIV, were downregulated, while apoptotic markers were upregulated in KO retinas. AQP4 may fine-tune synaptic activity, most likely by regulating potassium metabolism, at least in part, via collaborating with KIR2.1, and possibly indirectly regulating glutamate kinetics, to inhibit neural hyperactivity and synaptic fatigue which finally affect mitochondria and cause neurodegeneration.

  • Adrenergic receptor antagonism induces neuroprotection and facilitates recovery from acute ischemic stroke

    Monai H., Wang X., Yahagi K., Lou N., Mestre H., Xu Q., Abe Y., Yasui M., Iwai Y., Nedergaard M., Hirase H.

    Proceedings of the National Academy of Sciences of the United States of America (Proceedings of the National Academy of Sciences of the United States of America)  166 ( 22 ) 11010 - 11019 2019.05

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  00278424

     View Summary

    © 2019 National Academy of Sciences. All rights reserved. Spontaneous waves of cortical spreading depolarization (CSD) are induced in the setting of acute focal ischemia. CSD is linked to a sharp increase of extracellular K+ that induces a long-lasting suppression of neural activity. Furthermore, CSD induces secondary irreversible damage in the ischemic brain, suggesting that K+ homeostasis might constitute a therapeutic strategy in ischemic stroke. Here we report that adrenergic receptor (AdR) antagonism accelerates normalization of extracellular K+, resulting in faster recovery of neural activity after photothrombotic stroke. Remarkably, systemic adrenergic blockade before or after stroke facilitated functional motor recovery and reduced infarct volume, paralleling the preservation of the water channel aquaporin-4 in astrocytes. Our observations suggest that AdR blockers promote cerebrospinal fluid exchange and rapid extracellular K+ clearance, representing a potent potential intervention for acute stroke.

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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 (general), 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 (general)

  • 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 (general)

  • 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 (general)

  • 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 (general)

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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


    日本学術振興会, Grant-in-Aid for Scientific Research, 阿部陽一郎, 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


    日本学術振興会, Grant-in-Aid for Scientific Research, 阿部陽一郎, 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


    日本学術振興会, Grant-in-Aid for Scientific Research, 阿部陽一郎, 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


    日本学術振興会, Grant-in-Aid for Scientific Research, 阿部陽一郎, 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


    日本学術振興会, Grant-in-Aid for Scientific Research, 阿部陽一郎, Research grant, Principal Investigator

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Courses Taught 【 Display / hide







Courses Previously Taught 【 Display / hide

  • 薬理学

    Keio University, 2015, Spring Semester


Memberships in Academic Societies 【 Display / hide

  • 日本分子生物学会, 

  • 日本神経科学学会, 

  • Society for Neuroscience, 

  • 日本再生医療学会, 

  • 日本薬理学会,