慶應義塾研究者情報データベース

経歴 【 表示 ／ 非表示 】

経歴 【 表示 ／ 非表示 】

• 2004年10月

  -

  2007年03月

  Columbia University / Howard Hughes Medical Institute, 博士研究員

• 2007年04月

  -

  継続中

  慶應義塾大学, 医学部薬理学教室, 専任講師

• 2012年04月

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  継続中

  横浜国立大学, 環境情報学府, 客員准教授

• 2016年12月

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  継続中

  慶應義塾大学, 医学部薬理学教室, 准教授

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• 　

  The Johns Hopkins University, School of Medicine, Department of Neuroscience

  アメリカ合衆国, 大学院, 修了, 博士

• 　

  東京大学, 理学部, 生物化学科

  大学, 卒業

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• Ph.D., The Johns Hopkins University, 2004年

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• Label-Free Visualization of Ciliary Rootlets in Mouse Brain

  Murakami Y., Nuriya M., Hu Z., Tomioka M., Oketani R., Hiramatsu K., Leproux P., Inoko A., Honjoh S., Kano H.

  Analytical Chemistry 97 （ 27 ） 14160 - 14167 2025年07月

  ISSN  00032700

  　概要を見る

  Neuronal primary cilia play important roles in brain development, sensory perception, and neurogenesis. Rootletin, a fibrous protein composed of coiled-coil motifs, is a key structural component of ciliary rootlets and is essential for understanding ciliary functions. However, the precise mechanisms by which Rootletin influences ciliary dynamics and impacts neuronal function remain largely unknown, primarily due to the challenges associated with visualizing these structures. In this study, we present a label-free, rapid, and highly sensitive method for visualizing Rootletin molecules in brain tissue. This platform integrates a second harmonic generation (SHG) microscope with background reduction by a one-step chemical pretreatment. Additionally, we employed coherent anti-Stokes Raman scattering imaging to simultaneously determine the cellular regions and intracellular locations of SHG signals. Applying this multimodal multiphoton imaging approach to the mouse hippocampus revealed that neuronal ciliary rootlets exhibited highly organized and specific intracellular distributions. Moreover, measurements of cultured neurons revealed that ciliary rootlets were detected even in immature neurons. These findings highlight the utility of our label-free imaging platform in developmental and neuroscience research, providing a powerful tool for characterizing ciliary dynamics and neuronal function.

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• 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年07月

  ISSN  13478613

  　概要を見る

  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.

  • Access to Document (DOI)

• Spectral-focusing coherent anti-Stokes Raman scattering driven by bright correlated twin beams

  Eto Y., Nuriya M., Kano H.

  Physical Review Applied 23 （ 6 ）  2025年06月

  　概要を見る

  An understanding of the interaction between bright correlated twin beams and matter is important for expanding the applications of optical quantum technology. In particular, it is worthwhile to clarify the advantages of twin-beam correlation in spectroscopic applications, since twin-beam sources that use parametric down-conversion have a wide range of wavelength tunability. Here, we theoretically and experimentally demonstrate that the spectral-focusing technique used in coherent anti-Stokes Raman scattering (CARS) can be implemented by twin beams without the use of ultrashort-pulse lasers. In typical spectral focusing using ultrashort pulses, spectral resolution is improved by narrowing the instantaneous frequency width due to frequency chirping. Similarly, we show theoretically that the formation of a chirp structure within the temporal correlation of twin beams produces an effect similar to typical spectral focusing. To experimentally demonstrate twin-beam spectral focusing, CARS spectroscopy of polyethylene is performed when the time delay between the chirped twin beams is set within the correlation width or it is set outside the correlation width. We observe that the spectral resolution is improved when the correlation is effective. By comparing with theoretical simulations, we confirm that the improvement is caused by frequency chirping.

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• Molecular identification of second harmonic generation (SHG) sources in mouse brain by multimodal imaging with ultra-broadband multiplex coherent anti Stokes Raman scattering (CARS)

  Murakami Y., Oketani R., Leproux P., Nuriya M., Honjoh S., Hideaki K.

  Progress in Biomedical Optics and Imaging Proceedings of SPIE 12855 2024年

  ISSN  16057422

  　概要を見る

  Second harmonic generation imaging is a powerful tool for visualizing molecular structures in living organisms without the need for exogenous dyes. However, SHG signal lacks molecular specificity in identifying the source. This study aimed at molecular identification of SHG sources in the mouse brain using a multimodal imaging technique combining SHG and multiplex coherent anti Stokes Raman scattering (CARS) spectroscopy. We performed multimodal imaging in two different regions, the surface and dentate gyrus of the brain tissue. For the brain surface, the SHG signal was recognized through CARS spectrum analysis, indicating its origin in collagen. In the dentate gyrus, CARS images did not unveil corresponding molecular origins; however, morphologically, the SHG signal likely originated from Rootletin within neurons. Overall, Multimodal imaging approach to molecular identification of SHG has the potential to contribute to a comprehensive understanding of the molecular and structural features of the mouse brain. These findings advance label-free imaging techniques and have implications for brain tissue analysis and functional mapping research.

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• Stimulated Raman scattering microscopy reveals a unique and steady nature of brain water dynamics

  Shinotsuka T., Miyazawa T., Karasawa K., Ozeki Y., Yasui M., Nuriya M.

  Cell Reports Methods 3 （ 7 ）  2023年07月

  　概要を見る

  The biological activities of substances in the brain are shaped by their spatiotemporal dynamics in brain tissues, all of which are regulated by water dynamics. In contrast to solute dynamics, water dynamics have been poorly characterized, owing to the lack of appropriate analytical tools. To overcome this limitation, we apply stimulated Raman scattering multimodal multiphoton microscopy to live brain tissues. The microscopy system allows for the visualization of deuterated water, fluorescence-labeled solutes, and cellular structures at high spatiotemporal resolution, revealing that water moves faster than fluorescent molecules in brain tissues. Detailed analyses demonstrate that water, unlike solutes, diffuses homogeneously in brain tissues without differences between the intra- and the extracellular routes. Furthermore, we find that the water dynamics are steady during development and ischemia, when diffusions of solutes are severely affected. Thus, our approach reveals routes and uniquely robust properties of water diffusion in brain tissues.

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• アルキンタギングによる脳の病態生理学解明の新たなツールの開発と応用

  塗谷, 睦生

  科学研究費補助金研究成果報告書 2023年

• 組織内水のケミカルイメージングから迫る脳の生理学

  塗谷, 睦生

  科学研究費補助金研究成果報告書 2023年

• アストロサイトの構造機能連関とその制御の解明

  塗谷, 睦生

  科学研究費補助金研究成果報告書 2018年

• 次世代色素を用いた光第二高調波イメージングによる生体現象の可視化

  塗谷, 睦生

  科学研究費補助金研究成果報告書 2015年

• 第二高調波イメージングの応用による神経生理機能解析

  塗谷, 睦生

  科学研究費補助金研究成果報告書 2013年

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• Uses of coherent Raman scattering microscopy in neuroscience

  Nuriya M.

  Frontiers in Neuroscience 19 2026年

  ISSN  16624548

  　概要を見る

  Multiphoton microscopy allows the imaging of biological phenomena deep within brain tissues and has greatly advanced knowledge in neuroscience. However, many optical phenomena other than the multiphoton excitation of fluorophores in nonlinear optics are underrecognized. Coherent Raman scattering (CRS) uses multiple photons to boost weak Raman scattering. CRS has been used to enable molecular vibration-dependent contrast imaging of tissues and has been particularly useful for pathophysiological investigations of brain tissues. Recently, the combination of CRS with Raman-active bio-orthogonal chemical bonds or groups has proven particularly powerful for visualizing molecules not detectable by fluorescence imaging. This review introduces a new and exciting imaging strategy and its applications in neuroscience.

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競争的研究費の研究課題 【 表示 ／ 非表示 】

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• 化学情報伝達の直接的可視化解析

  2024年06月

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  2026年03月

  塗谷 睦生, 挑戦的研究（萌芽）, 補助金,  研究代表者

• 新規可視化法の開発と応用による微視的薬物動態の解明

  2024年04月

  -

  2027年03月

  塗谷 睦生, 基盤研究(B), 補助金,  研究代表者

• 組織内水のケミカルイメージングから迫る脳の生理学

  2020年07月

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  2024年03月

  文部科学省・日本学術振興会, 科学研究費助成事業, 塗谷 睦生, 挑戦的研究（開拓）, 補助金,  研究代表者

• アルキンタギングによる脳の病態生理学解明の新たなツールの開発と応用

  2020年04月

  -

  2024年03月

  文部科学省・日本学術振興会, 科学研究費助成事業, 塗谷 睦生, 基盤研究(B), 補助金,  研究代表者

• アストロサイトの構造機能連関とその制御の解明

  2016年04月

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  2019年03月

  文部科学省・日本学術振興会, 科学研究費助成事業, 塗谷　睦生, 基盤研究(C), 補助金,  研究代表者

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• 薬理学

  2025年度

• 薬理学

  2024年度

• 薬理学

  2023年度

• 薬理学

  2022年度

• 薬理学

  2021年度

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• MCB-I

  慶應義塾

  2015年04月

  -

  2016年03月

• 基礎分子細胞学

  慶應義塾

  2015年04月

  -

  2016年03月

• 薬理学

  慶應義塾

  2015年04月

  -

  2016年03月