田中 謙二 (タナカ ケンジ)

Tanaka, Kenji

写真a

所属(所属キャンパス)

医学部 精神・神経科学教室 (信濃町)

職名

准教授

メールアドレス

メールアドレス

HP

外部リンク

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  • 1991年 麻布高校卒
    1997年 慶應義塾大学医学部卒
    2003年 慶應義塾大学大学院修了
    2016年 慶應義塾大学医学部精神神経科学 准教授
    2019年 慶應義塾大学体育会アメリカンフットボール部 部長

教員からのメッセージ 【 表示 / 非表示

  • 気合い

学位 【 表示 / 非表示

  • 博士(医学), 慶應義塾, 課程, 2003年03月

免許・資格 【 表示 / 非表示

  • 医師免許, 1997年04月

 

研究分野 【 表示 / 非表示

  • 神経化学・神経薬理学

研究キーワード 【 表示 / 非表示

  • FASTシステム

  • KENGE-tet

  • ファイバーフォトメトリー法

  • 光遺伝学

  • 意欲

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  • Cathepsin C modulates myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis

    Durose W., Shimizu T., Li J., Abe M., Sakimura K., Chetsawang B., Tanaka K., Suzumura A., Tohyama K., Ikenaka K.

    Journal of Neurochemistry (Journal of Neurochemistry)  148 ( 3 ) 413 - 425 2019年02月

    ISSN  00223042

     概要を見る

    © 2018 International Society for Neurochemistry Multiple sclerosis (MS) is an autoimmune disease characterized by immune-mediated inflammation, which attacks the myelin sheath. MS pursues a relapsing and remitting course with varying intervals between symptoms. The main clinical pathological features include inflammation, myelin sheath destruction and plaque formation in the central nervous system (CNS). We previously reported that cystatin F (CysF) expression is induced in demyelinating lesions that are accompanied by active remyelination (referred to as shadow plaques) but is down-regulated in chronic demyelinated lesions (plaques) in the spinal cord of MS patients and in several murine models of demyelinating disease. CysF is a cathepsin protease inhibitor whose major target is cathepsin C (CatC), which is co-expressed in demyelinating regions in Plp 4e/− mice, a model of chronic demyelination. Here, we report the time course of CatC and CysF expression and describe the symptoms in a mouse experimental autoimmune encephalomyelitis (EAE) model using CatC knockdown (KD) and CatC over-expression (OE) mice. In myelin oligodendrocyte glycoprotein (MOG)-EAE, CatC positive cells were found to infiltrate the CNS at an early stage prior to any clinical signs, in comparison to WT mice. CysF expression was not observed at this early stage, but appeared later within shadow plaques. CatC expression was found in chronic demyelinated lesions but was not associated with CysF expression, and CatCKD EAE mouse showed delayed demyelination. Whereas, CatCOE in microglia significantly increased severity of demyelination in the MOG-EAE model. Thus, these results demonstrate that CatC plays a major role in MOG-EAE. (Figure presented.).

  • Mechanical regulation of oligodendrocyte morphology and maturation by the mechanosensor p130Cas

    Shimizu T., Osanai Y., Tanaka K., Thai T., Abe M., Natsume R., Sakimura K., Ikenaka K.

    Journal of Neurochemistry (Journal of Neurochemistry)  2019年

    ISSN  00223042

     概要を見る

    © 2018 International Society for Neurochemistry Oligodendrocytes (OLs) are myelinating cells of the central nervous system. Recent studies have shown that mechanical factors influence various cell properties. Mechanical stimulation can be transduced into intracellular biochemical signals through mechanosensors, such as integrin, p130Cas, talin and vinculin. However, the molecular mechanisms underlying the mechanical regulation of OLs by mechanosensors remain largely unknown. We found that morphology of OL was affected by knockdown of the mechanosensors p130Cas or talin1. Stretching of OL precursor cells induced the phosphorylation of p130Cas and talin-associated assembly of vinculin. Shear stress decreased the number of OL processes, whereas these effects were mechanically suppressed by dominant-negative (DN) p130Cas, but not by DN-talin1. To investigate the roles of p130Cas in post-natal OLs in vivo, we constructed a novel p130Cas knock-in mouse and found overexpression of p130Cas in vivo affected the number of mature OLs in the cortex. These results indicate that the mechanosensor p130Cas controls both OL morphogenesis and maturation. (Figure presented.).

  • Reward probability and timing uncertainty alter the effect of dorsal raphe serotonin neurons on patience

    Miyazaki K., Miyazaki K., Yamanaka A., Tokuda T., Tanaka K., Doya K.

    Nature Communications (Nature Communications)  9 ( 1 )  2018年12月

     概要を見る

    © 2018 The Author(s). Recent experiments have shown that optogenetic activation of serotonin neurons in the dorsal raphe nucleus (DRN) in mice enhances patience in waiting for future rewards. Here, we show that serotonin effect in promoting waiting is maximized by both high probability and high timing uncertainty of reward. Optogenetic activation of serotonergic neurons prolongs waiting time in no-reward trials in a task with 75% food reward probability, but not with 50 or 25% reward probabilities. Serotonin effect in promoting waiting increases when the timing of reward presentation becomes unpredictable. To coherently explain the experimental data, we propose a Bayesian decision model of waiting that assumes that serotonin neuron activation increases the prior probability or subjective confidence of reward delivery. The present data and modeling point to the possibility of a generalized role of serotonin in resolving trade-offs, not only between immediate and delayed rewards, but also between sensory evidence and subjective confidence.

  • Visualization of myelinated fiber bundles orientation during brain slice preparation by reflection polarized light microscopy

    Takata N., Kusayanagi K., Maruyama H., Eitai K., Abo M., Akiyama F., Tajima R., Inaba S., Tanaka K., Mimura M., Sanaka K.

    Microscopy Research and Technique (Microscopy Research and Technique)  81 ( 12 ) 1366 - 1373 2018年12月

    ISSN  1059910X

     概要を見る

    © 2018 Wiley Periodicals, Inc. Polarized light imaging (PLI) enables detecting the orientation of myelinated axon bundles in brain slices at microscopic resolution without histological staining. However, standard PLI requires labor-intensive procedures such as mounting brain cryosections on slide glasses. We developed an optical system that does not require a mounting procedure for PLI. Specifically, we developed an optical system to perform PLI in reflection mode (rPLI) instead of employing transmitted light as in standard PLI. We integrated this rPLI system with a conventional vibratome slicer whose cutting blade surface is a mirror. This combination allowed PLI measurements directly during the slicing procedure at room temperature. Thus, mounting procedure for PLI is not necessary. As a proof-of-concept experiment, a perfusion-fixed brain of a mouse was embedded in gelatin-containing agar and cut serially at 40~200 μm intervals. The slicing procedure was temporarily halted after each cut to capture the PLI images of the slice on the reflecting blade surface while the slice was still held up by the agar block. The orientation of the fiber bundle estimated with this method agreed with the results obtained from previous reports. Combination of a popular vibratome slicer and our rPLI system that uses versatile and inexpensive optical components would increase popularity of PLI and facilitates connectome studies at microscopic resolution. Research Highlights: Polarized light imaging (PLI) of brain slices was realized by using reflected light (rPLI) instead of transmitted light. The rPLI method allows detecting the myelinated fiber bundle orientation during slice preparation.

  • Ectopic positioning of Bergmann glia and impaired cerebellar wiring in Mlc1-over-expressing mice

    Kikuchihara S., Sugio S., Tanaka K., Watanabe T., Kano M., Yamazaki Y., Watanabe M., Ikenaka K.

    Journal of Neurochemistry (Journal of Neurochemistry)  147 ( 3 ) 344 - 360 2018年11月

    ISSN  00223042

     概要を見る

    © 2018 International Society for Neurochemistry Mlc1 is a causative gene for megalencephalic leukoencephalopathy with subcortical cysts, and is expressed in astrocytes. Mlc1-over-expressing mice represent an animal model of early-onset leukoencephalopathy, which manifests as astrocytic swelling followed by myelin membrane splitting in the white matter. It has been previously reported that Mlc1 is highly expressed in Bergmann glia, while the cerebellar phenotypes of Mlc1-over-expressing mouse have not been characterized. Here, we examined the cerebellum of Mlc1-over-expressing mouse and found that the distribution of Bergmann glia (BG) was normally compacted along the Purkinje cell (PC) layer until postnatal day 10 (P10), while most BG were dispersed throughout the molecular layer by P28. Ectopic BG were poorly wrapped around somatodendritic elements of PCs and exhibited reduced expression of the glutamate transporter glutamate-aspartate transporter. Extraordinarily slow and small climbing fiber (CF)-mediated excitatory post-synaptic currents, which are known to be elicited under accelerated glutamate spillover, emerged at P20-P28 when BG ectopia was severe, but not at P9-P12 when ectopia was mild. Furthermore, maturation of CF wiring, which translocates the site of innervation from somata to proximal dendrites, was also impaired. Manipulations that restricted the Mlc1-over-expressing period successfully generated mice with and without BG ectopia, depending on the over-expressing period. Together, these findings suggest that there is a critical time window for mechanisms that promote the positioning of BG in the PC layer. Once normal positioning of BG is affected, the differentiation of BG is impaired, leading to insufficient glial wrapping, exacerbated glutamate spillover, and aberrant synaptic wiring in PCs. Open Practices Open Science: This manuscript was awarded with the Open Materials Badge. For more information see: https://cos.io/our-services/open-science-badges/. (Figure presented.). Cover Image for this issue: doi: 10.1111/jnc.14199.

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研究発表 【 表示 / 非表示

  • the 5th BRI International Symposium: Genome editing technology; its status quo and application to brain research

    田中 謙二

    the 5th BRI International Symposium: Genome editing technology; its status quo and application to brain research, 2015年03月, 口頭(一般)

  • 特定細胞集団の活動を操作する、観察する

    田中 謙二

    都医学研セミナー (東京都医学総合研究所 講堂) , 2015年01月, 公開講演,セミナー,チュートリアル,講習,講義等, 東京都医学総合研究所

  • 第25回マイクロダイアリシス研究会

    田中 謙二

    第25回マイクロダイアリシス研究会, 2014年12月, 口頭(一般)

  • 精神医学研究にオプトジェネティクスが期待されること

    田中 謙二

    第35回日本レーザー医学会総会, 2014年11月, 口頭(招待・特別)

  • ミクログリアはP2Y1受容体制御により神経保護的アストロサイトを誘導する

    田中 謙二

    第57回日本神経化学会大会 (奈良県文化会館) , 2014年09月, 口頭(一般)

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競争的資金等の研究課題 【 表示 / 非表示

  • 意欲行動の持続にかかわる神経基盤の解明

    2019年04月
    -
    2021年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 田中 謙二, 新学術領域研究(研究課題提案型), 補助金,  代表

  • 負に立ち向かうウィルパワーをつかさどる神経基盤の解明

    2017年04月
    -
    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, 田中 謙二, 新学術領域研究(研究領域提案型), 補助金,  代表

  • 線条体におけるカルシウム振動の描出と生理学的意義の解明

    2016年04月
    -
    2018年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 田中 謙二, 新学術領域研究(研究領域提案型), 補助金,  代表

  • 情動を制御するBDNFの直接効果の解明

    2015年04月
    -
    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, 田中 謙二, 基盤研究(B), 補助金,  代表

Works 【 表示 / 非表示

  • 夏休みの研究体験

    2013年07月
    -
    2013年08月

    その他, 単独

     発表内容を見る

    4日間にわたって、脳科学研究実習、精神科臨床見学(NIRSの実体験含む)、解剖学教室見学などを行った。

  • ゆとりの時間「Let's Enjoy High School Science」

    田中謙二

    2013年07月
    -
    継続中

    その他, 単独

     発表内容を見る

    慶應義塾湘南藤沢高等部 1年生の生物選択の生徒対象 

 

担当授業科目 【 表示 / 非表示

  • 精神医学講義

    2019年度

  • MCB

    2019年度

  • 生理学Ⅰ

    2019年度