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KUMAMOTO Natsuko

    Graduate School of Medical Sciences Department of Anatomy and Neuroscience　Lecturer
Last Updated :2024/06/11

Researcher Information

J-Global ID

Research Interests

  • 感覚器   ASICs   Primary cilia   Adult neurogenesis   

Research Areas

  • Life sciences / Anatomy

Association Memberships

  • THE JAPAN NEUROSCIENCE SOCIETY   THE JAPANESE SOCIETY FOR NEUROCHEMISTRY   THE JAPANESE ASSOCIATION OF ANATOMISTS   

Published Papers

MISC

  • Primary cilia in brain function and disease
    Natsuko Kumamoto  Kidney and dialysis  87-  (5)  713  -716  2019/11  [Invited]
  • 脳の一次繊毛
    熊本 奈都子  実験医学  36-  (6)  938  -943  2018/04  [Invited]
  • シリア（神経細胞のヒゲ）
    熊本 奈都子  脳２１  15-  (3)  98  -102  2012  [Invited]
  • 繊毛異常と神経難病
    熊本 奈都子  脳２１  16-  (3)  78  -82  2012  [Invited]

Research Grants & Projects

  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2022/04 -2027/03 
    Author : 鵜川 眞也; 岩崎 真一; 柴田 泰宏; 島田 昌一; 熊本 奈都子; 村上 信五; 植田 高史
  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2020/04 -2023/03 
    Author : 熊本 奈都子; 鵜川 眞也; 澤本 和延
     
    ASIC1aは水素イオンで開く陽イオンチャネルであり、脳では、神経細胞に発現し、シナプス小胞から神経伝達物質とともに開口放出された水素イオンをシナプス後膜にて受容することで、神経情報伝達に関与している。一方、虚血時には、嫌気性解糖の亢進により病変局所に水素イオンが蓄積するが、これに応答して開いたASIC1aは、細胞内へ陽イオンを流入させ、細胞の興奮に働く。虚血時に活性化されたASIC1aが成体脳海馬神経新生にどのような影響を与えるかを明らかにする。我々はまず、新生ニューロン特異的ASKC1a欠損マウスを用い、ASIC1aが虚血脳において神経幹/前駆細胞の増殖、生存に与える影響を検討した。新生ニューロン特異的ASIC1a欠損マウス（Nestin-CreERT2/lox-ASIC1a-loxマウス）にTMX（タモキシフェン）を5日間連続腹腔内投与し、神経幹/前駆細胞のASIC1aを欠損させた。最後のTMX投与の3日後に左側中大脳動脈永久閉塞MCAOを行って梗塞巣を作製した。その3日後にBrdUを単回腹腔内投与し、2時間後に脳を摘出、BrdUの蛍光免疫染色を行い、BrdU陽性（増殖）細胞の数を評価した。同様の脳虚血モデルマウスを用い、12時間ごとにBrdUを計6回 腹腔内投与し、BrdU最終投与から28日後に脳を摘出、BrdUの蛍光免疫染色を行い、BrdU陽性細胞（生存細胞）の数をカウントした。MCAOでは中大脳動脈支配領域である線条体と大脳皮質に梗塞巣が形成されるが、C57BL6系マウスは梗塞巣の大きさにばらつきがあり、データに個体差があるため、現在N数を増やして野生型マウスの脳虚血モデルマウスと比較検討中である。
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2017/04 -2021/03 
    Author : Ugawa Shinya
     
    ASICs (acid-sensing ion channels) are putative mechano-gated cation channels in mammals. In the present study, we discovered that at least ASIC1a, ASIC1b, and ASIC4 are expressed in mouse auditory and vestibular hair cells. In particular, transmission electron microscopy revealed that ASIC1b proteins were located at the stereociliary tips, suggesting that all the three ASIC subtypes are somehow involved in the generation of mechanoelectrical transduction (MET) currents. ABR (auditory brainstem response) tests demonstrated the slight-to-moderate degree of deafness in ASIC1b or ASIC4 knockout mice. Further investigations are needed to assess the physiological roles of ASICs in mouse inner ear MET.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2016/04 -2020/03 
    Author : Kumamoto Natsuko
     
    ASIC1a (acid-sensing ion channel-1a) is an ion channel activated by extracellular protons. Immunohistochemical analysis of TagRFP-V5-ASIC1a knock-in mice, in which TagRFP-V5 tagged ASIC1a is expressed under the control of the endogenous ASIC1a gene promoter, showed that ASIC1a is expressed in new-born neurons from early stage of adult hippocampal neurogenesis onwards. In addition, ASIC1a knockdown induced defects in dendritic refinement and spine formation. Similar results were found following intracerebroventricular injection of ASIC1a antagonist. The data indicate that ASIC1a could regulate adult hippocampal neurogenesis under normal condition.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2017/06 -2019/03 
    Author : Ugawa Shinya
     
    We identified a putative mechanosensory channel ASIC-X in mouse auditory hair cells, and explored its channel properties using a combination of electrophysiology and ratio-imaging techniques with fura-2 and SBFI. Although the leakage currents of heterologously expressed ASIC-X were augmented by strong shear stress, neither hypotonicity nor direct stretching of plasma membrane enhanced the currents. Mechanoelectrical transduction (MET) currents in outer hair cells (OHCs) of ASIC-X knockout mice did not significantly change in the amplitude, compared to MET currents in wild-type OHCs, which is in good agreement with the in vitro data. However, our investigations revealed that the ASIC-X channel was selective to sodium ions. Therefore, ASIC-X is most likely to function as a sodium leak channel in vivo rather than as a mechanosensitive molecule. The tissue distribution of the channel should be clarified in detail next.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2013/04 -2016/03 
    Author : Kumamoto Natsuko
     
    It is well known that adult neurogenesis is enhanced after ischemic brain injury accompanied with local tissue acidosis. However, the molecular mechanisms mediating such phenomena remain to be elucidated. ASIC1a (acid-sensing ion channel-1a) is an ion channel activated by extracellular protons. Using a combination of morphological and electrophysiological approaches, we found that ASIC1a was required for proper dendritic development and synaptic organization of mouse hippocampal newborn neurons. These results raise the possibility that ASIC1a might regulate adult hippocampal neurogenesis via sensing extracellular acidification during cerebral ischemia. Definitive understandings of roles of ASIC1a in adult neurogenesis will contribute to development of non-invasive nerve repair treatments through activation of endogenous neural stem cells in the brain.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2011 -2012 
    Author : KUMAMOTO Natsuko
     
    DISC1 knockdown using onco-retrovirus-mediated approach to genetically label and manipulate neural stem cells in adult mouse hippocampus resulted in defective primary cilia formation in vivo. Loss-of- function mutations of β-catenin in newborn neurons reversed the accelerated neuronal migration and dendritic development caused by the DISC1 knockdown.

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