YAMADA Takashi

写真a

Affiliation

School of Health Science, Department of Physical Therapy, First Division of Physical Therapy

Job title

Associate Professor
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Degree 【 display / non-display 】

  • 広島大学大学院   博士（保健学）

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Research Experience 【 display / non-display 】

  • 2016.04
    -
    Now

    Sapporo Medical University   School of Health Sciences, Department of Physical Therapy  

  • 2011.05
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    2016.03

    Sapporo Medical University   School of Health Sciences, Department of Physical Therapy  

  • 2010.04
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    2011.04

    Sapporo Medical University   School of Health Sciences, Department of Physical Therapy  

  • 2007.04
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    2010.03

    Karolinska Institutet  

  • 2006.04
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    2007.03

    Hiroshima University   Graduate School of Integrated Arts and Sciences  

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Research Areas 【 display / non-display 】

  • Life sciences   Neuroscience - general  

  • Life sciences   Nutrition and health science  

  • Life sciences   Clinical pharmacy  

  • Life sciences   Physiology  

  • Life sciences   Rehabilitation science  

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Affiliation 【 display / non-display 】

  • 札幌医科大学   保健医療学部 理学療法学科   准教授  

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Research Interests 【 display / non-display 】

  • 興奮収縮連関

  • メカニカルストレス

  • Neuromuscular electrical stimulation

  • 骨格筋

  • Muscle weakness

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Papers 【 display / non-display 】

  • Platelet-rich plasma does not accelerate the healing of damaged muscle following muscle strain.

    Hiroyori Fusagawa, Takashi Yamada, Tatsuya Sato, Yuki Ashida, Atsushi Teramoto, Hiroyuki Takashima, Azuma Naito, Nao Tokuda, Nao Yamauchi, Nobutoshi Ichise, Izaya Ogon, Toshihiko Yamashita, Noritsugu Tohse

    Journal of orthopaedic research : official publication of the Orthopaedic Research Society    2024.01  [Refereed]  [International journal]

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    Although platelet-rich plasma (PRP) has been widely used regardless of the severity of muscle strain, there have been very few basic studies in which its effects on muscle injury were examined by using models that accurately mimic the clinical muscle strain injury process. Therefore, the aim of this study was to confirm by physiological and structural analyses whether PRP purified by a general preparation method has a muscle healing effect on muscle damage caused by eccentric contraction (ECC). Male Wistar rats were subjected to muscle injury induced by ECC in bilateral plantar flexor muscles using electrical stimulation and an automatically dorsiflexing footplate. The rats were randomly assigned to three groups by type of injection: phosphate-buffered saline (PBS), leukocyte-poor PRP (LP-PRP), or leukocyte-rich PRP (LR-PRP) injection into gastrocnemius muscles three times at weekly intervals. The platelet concentrations of the LP-PRP and LR-PRP were three to five times higher than that of whole blood. The recovery process of torque strength in the plantar flexor muscle, signal changes in MRI images, and histological evaluation 3 weeks after injury showed no obvious differences among the three groups, and every muscle recovered well from the injury without marked fibrosis. The results that neither LP-PRP nor LR-PRP was found to accelerate healing of muscle injuries suggested that conventional preparation and use of PRP for simple muscle injuries caused by muscle strain should be carefully considered, and further basic research using models that accurately mimic clinical practice should be carried out to determine the optimal use of PRP.

    DOI PubMed

  • ジストロフィン欠損筋に対する等尺性収縮トレーニングにおける収縮強度の役割

    山内 菜緒, 内藤 雷, 徳田 奈央, 芦田 雪, 青木 吉嗣, 山田 崇史

    基礎理学療法学 ( (一社)日本基礎理学療法学会 )  26 ( Suppl.1 ) 79 - 79  2024.01

  • High-intensity interval training using electrical stimulation ameliorates muscle fatigue in chronic kidney disease-related cachexia by restoring mitochondrial respiratory dysfunction.

    Hiroyori Fusagawa, Tatsuya Sato, Takashi Yamada, Azuma Naito, Nao Tokuda, Nao Yamauchi, Nobutoshi Ichise, Toshifumi Ogawa, Takuro Karaushi, Atsushi Teramoto, Noritsugu Tohse

    Frontiers in physiology   15   1423504 - 1423504  2024  [Refereed]  [International journal]

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    BACKGROUND: Exercise, especially high-intensity interval training (HIIT), can increase mitochondrial respiratory capacity and enhance muscular endurance, but its systemic burden makes it difficult to safely and continuously prescribe for patients with chronic kidney disease (CKD)-related cachexia who are in poor general condition. In this study, we examined whether HIIT using electrical stimulation (ES), which does not require whole-body exercise, improves muscle endurance in the skeletal muscle of 5/6 nephrectomized rats, a widely used animal model for CKD-related cachexia. METHODS: Male Wistar rats (10 weeks old) were randomly assigned to a group of sham-operated (Sham) rats and a group of 5/6 nephrectomy (Nx) rats. HIIT was performed on plantar flexor muscles in vivo with supramaximal ES every other day for 4 weeks to assess muscle endurance, myosin heavy-chain isoforms, and mitochondrial respiratory function in Nx rats. A single session was also performed to identify upstream signaling pathways altered by HIIT using ES. RESULTS: In the non-trained plantar flexor muscles from Nx rats, the muscle endurance was significantly lower than that in plantar flexor muscles from Sham rats. The proportion of myosin heavy chain IIa/x, mitochondrial content, mitochondrial respiratory capacity, and formation of mitochondrial respiratory supercomplexes in the plantaris muscle were also significantly decreased in the non-trained plantar flexor muscles from Nx rats than compared to those in plantar flexor muscles from Sham rats. Treatment with HIIT using ES for Nx rats significantly improved these molecular and functional changes to the same degrees as those in Sham rats. Furthermore, a single session of HIIT with ES significantly increased the phosphorylation levels of AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (MAPK), pathways that are essential for mitochondrial activation signaling by exercise, in the plantar muscles of both Nx and Sham rats. CONCLUSION: The findings suggest that HIIT using ES ameliorates muscle fatigue in Nx rats via restoration of mitochondrial respiratory dysfunction with activation of AMPK and p38 MAPK signaling. Our ES-based HIIT protocol can be performed without placing a burden on the whole body and be a promising intervention that is implemented even in conditions of reduced general performance status such as CKD-related cachexia.

    DOI PubMed

  • Skeletal muscle endurance declines with impaired mitochondrial respiration and inadequate supply of acetyl-CoA during muscle fatigue in 5/6 nephrectomized rats.

    Hiroyori Fusagawa, Tatsuya Sato, Takashi Yamada, Yuki Ashida, Iori Kimura, Azuma Naito, Nao Tokuda, Nao Yamauchi, Nobutoshi Ichise, Yoshinori Terashima, Izaya Ogon, Atsushi Teramoto, Toshihiko Yamashita, Noritsugu Tohse

    Journal of applied physiology (Bethesda, Md. : 1985)   135   731 - 746  2023.08  [Refereed]  [International journal]

    Authorship：   Lead author

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    Chronic kidney disease (CKD)-related cachexia increases the risks of reduced physical activity and mortality. However, the physiological phenotype of skeletal muscle fatigue and changes in intramuscular metabolites during muscle fatigue in CKD-related cachexia remain unclear. In the present study, we performed detailed muscle physiological evaluation, analysis of mitochondrial function, and comprehensive analysis of metabolic changes before and after muscle fatigue in a 5/6 nephrectomized rat model of CKD. Wistar rats were randomized to a sham-operation (Sham) group that served as a control group or a 5/6 nephrectomy (Nx) group. Eight weeks after the operation, in situ torque and force measurements in plantar flexor muscles in Nx rats using electrical stimulation revealed a significant decrease in muscle endurance during subacute phase related to mitochondrial function. Muscle mass was reduced without changes in the proportions of fiber type-specific myosin heavy chain isoforms in Nx rats. Pyruvate-malate-driven state 3 respiration in isolated mitochondria were impaired in Nx rats. Protein expression levels of mitochondrial respiratory chain complexes III and V were decreased in Nx rats. Metabolome analysis revealed that the increased supply of acetyl CoA in response to fatigue was blunted in Nx rats. These findings suggest that CKD deteriorates skeletal muscle endurance in association with mitochondrial dysfunction and inadequate supply of acetyl-CoA during muscle fatigue.

    DOI PubMed

  • Intrinsic contractile dysfunction due to impaired sarcoplasmic reticulum Ca2+ release in compensatory hypertrophied muscle fibers following synergist ablation.

    Nao Tokuda, Daiki Watanabe, Azuma Naito, Nao Yamauchi, Yuki Ashida, Arthur J Cheng, Takashi Yamada

    American journal of physiology. Cell physiology   325   C599 - C612  2023.07  [Refereed]  [International journal]

    Authorship：   Last author  , Corresponding author

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    Synergist ablation (SA) is an experimental procedure for the induction of hypertrophy. However, SA causes a decrease in specific force (i.e., force per cross-sectional area), likely due to excessive muscle use. Here, we investigated the mechanisms behind the SA-induced intrinsic contractile dysfunction, especially focusing on the excitation-contraction (EC) coupling. Male Wistar rats had unilateral surgical ablation of gastrocnemius and soleus muscles to induce the compensatory hypertrophy in the plantaris muscles. Two weeks after SA, plantaris muscle was dissected from each animal and used for later analyses. SA significantly increased the mean fiber cross-sectional area (+18%). On the other hand, the ratio of depolarization-induced force to the maximum Ca2+-activated specific force, an indicator of sarcoplasmic reticulum (SR) Ca2+ release, were markedly reduced in mechanically skinned fibers from the SA group (-51%). These functional defects were accompanied by an extensive fragmentation of the SR Ca2+ release channel, the ryanodine receptor 1 (RyR1), and a decrease in the amount of other triad proteins (i.e., DHPR, STAC3, and junctophilin1). SA treatment also caused an activation of calpain-1 and increased the amount of NADPH oxidase 2, ER stress proteins (i.e., Grp78, Grp94, PDI and Ero1), and lipid peroxidation (i.e., 4-HNE) in SA-treated muscles. Our findings show that SA causes skeletal muscle weakness due to impaired EC coupling. This is likely to be induced by Ca2+-dependent degradation of triad proteins, which may result from Ca2+ leak from fragmented RyR1 triggered by increased oxidative stress.

    DOI PubMed

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Books and Other Publications 【 display / non-display 】

  • Sarcopenia, Molecular Mechanism and Treatment Strategies

    Takashi Yamada( Part： Contributor, Mechanisms of decline in muscle quality in sarcopenia)

    Elsevier  2021.07

  • Muscle biophysics. From molecule to cells. Chapter 16, Mechanisms of skeletal muscle weakness.

    Advances in Experimental Medicine and Biology. Vol. 682, Springer  2010 ISBN: 9781441963659

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Misc 【 display / non-display 】

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Awards 【 display / non-display 】

  • 学術大会長賞

    2022.10   第27回日本基礎理学療法学会学術大会   等尺性トレーニングはDMDモデルマウスの筋病変を改善する

    Winner： 山内 菜緒, 内藤 雷, 德田 奈央, 木村 伊織, 芦田 雪, 青木 吉嗣, 山田 崇史

  • 最優秀論文賞

    2022.03   基礎理学療法学   ストレッチは脱神経後早期における骨格筋の興奮性低下を軽減する

    Winner： 芦田 雪, 渡邊 大輝, 宮田 浩文, 檜森 弘一, 玉井 勝是, 木村 伊織, 阿部 真佐美, 今井 富裕, 山田 崇史

  • 優秀論文賞

    2019.12   日本基礎理学療法学会   神経筋電気刺激療法とグルタミン投与の併用がcolon 26がんモデルマウスにおける筋萎縮に及ぼす影響

    Winner： 舘林大介, 檜森弘一, 芦田雪, 山田崇史

  • 優秀論文賞

    2017.11   日本基礎理学療法学会   神経筋電気刺激誘引性の筋肥大における負荷強度と力積の役割

    Winner： 檜森弘一, 舘林大介, 大山友加, 青木達彦, 山田崇史

  • 優秀論文賞

    2016.09   日本基礎理学療法学会   熱刺激がモノクロタリン誘発性肺高血圧症ラットの横隔膜における収縮機能に及ぼす影響

    Winner： 阿部真佐美, 李宰植, 舘林大介, 檜森弘一, 山田崇史

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Research Projects 【 display / non-display 】

  • 腎不全サルコペニアの運動時エネルギー代謝障害の解明と神経-筋電気刺激療法の確立

    基盤研究(C)

    Project Year :

    2023.04
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    2026.03
     

    房川 祐頼, 佐藤 達也, 山田 崇史

  • 蛋白アセチル化修飾を標的としたサルコペニア発症機序の解明と治療法開発

    基盤研究(C)

    Project Year :

    2022.04
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    2025.03
     

    細田 隆介, 岩原 直敏, 藤谷 直樹, 野島 伊世里, 久野 篤史, 山田 崇史

  • 骨格筋の肥大適応における筋幹細胞と免疫細胞の連関

    挑戦的研究(萌芽)

    Project Year :

    2021.07
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    2024.03
     

    山田 崇史

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    本研究の全体構想は，骨格筋の肥大応答における筋サテライト細胞の役割とその制御機構の解明である．2021年度には，課題1「非損傷性の運動による筋肥大における筋サテライト細胞の役割」として，筋サテライト細胞の欠損（Pax7-DTA）マウスを導入し，トレーニングによる筋肥大応答を検討する予定であった．しなしながら，Pax7-DTAマウスの凍結胚の個体復元がうまく行かず，2021年度内に当該マウスを本学に導入することができなかった．そこで，予定を変更し，2021年度には事前準備として筋肥大モデルの妥当性の検討を行うこととした．小動物において，協働筋切除法は，簡便に筋線維の肥大を誘引できるため広く用いられている．ただし，この方法は，運動によるヒト骨格筋の肥大適応に比べ，短期間で急激な肥大をもたらすことから，外挿性の低さが指摘されている．本研究では，協働筋切除による筋肥大の表現型について，特に収縮機能に焦点をあて検討した．ラット足底筋では，協働筋切除による2週間の代償性過負荷により，筋重量および筋線維径が増大した．一方，ex vivoにおける全筋の固有張力（発揮張力を筋重量で補正した値）および単一筋線維（スキンドファイバー）における脱分極誘発性ならびに最大Ca2+誘発性張力の低下が観察された．したがって，これらの知見から，協働筋切除では，過負荷により筋線維の肥大が誘引される一方，過用により興奮収縮連関および筋原線維機能の障害が引き起こされることが示唆された．

  • 橋渡し研究の推進による特発性炎症性ミオパチー克服へ向けた運動処方の基盤創出

    基盤研究(B)

    Project Year :

    2021.04
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    2025.03
     

    山田 崇史

    　View Summary

    本研究の全体構想は，特発性炎症性ミオパチーに対する安全で効果的な運動処方の基盤創出である．2021年度には，課題1「高強度間欠的運動の神経-筋電気刺激への応用と作用メカニズム解明」の実験1として，正常マウスに対する神経-筋電気刺激（ES）を用いた間欠的運動（IT）の効果を検証した．11～12週齢のマウスの下腿三頭筋に対し，高強度（100 Hz，IT100群）あるいは低強度（20 Hz，IT20群）のESによるITを，2日に1回の頻度で4週間負荷した．最終IT負荷の48時間後に，足底筋，腓腹筋を採取し，生化学的解析に供した．結果，両群とも，ミトコンドリア量の指標であるクエン酸合成酵素（CS）活性ならびにミトコンドリア生合成の制御因子であるPGC-1αの発現量が増大したが，その増加率に群間で差は認められなかった．一方，IT100においてのみ，呼吸鎖複合体I，III，IVの発現量およびスーパーコンプレックスの形成量増加とともに，ADP誘発性ミトコンドリア酸素消費速度の増大が観察された．したがって，ITにおいて，収縮強度の増大は，ミトコンドリアの量よりもむしろ機能（質）の向上に寄与する可能性が示唆された．また，当初の予定では，課題1：実験2として，ITによる持久力改善効果におけるPGC-1αの役割を，PGC-1α欠損動物を用い検討する予定であった．しかしながら，導入した動物の繁殖が思うように進まず，実験を遂行することができなかった．一方，課題2「特発性炎症性ミオパチー（IIM）に対する高強度間欠的運動の効果検証」に関しては，急性期のIIMモデルとして広く用いられている実験的自己免疫性ミオパチー（EAM）マウスを用い，ESによる高強度のITの効果検証を実施し，我々の期待通り，高強度のITがEAMマウスの疲労耐性を改善することが明らかとなった．

  • オートファジー基質が制御するマイオカインの同定と応用

    基盤研究(B)

    Project Year :

    2021.04
    -
    2025.03
     

    奥津 光晴, 山田崇史, 岩田全広

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    2021年度は、運動が骨格筋のオートファジー基質を活性化するマイオカインを探索した。方法は、野生型マウスに運動を実施し、オートファジー基質の活性化を制御するマイオカインを探索した。マウスは運動群と安静群に分け、運動群は自発走行運動を4週間実施し、安静群はその間通常飼育した。運動期間中はマウスの走行距離を測定し、自発走行運動が適切に実施されていることを確認した。運動期間終了後、マウスから血液と走行運動の主動筋である腓腹筋を採取した。採取は、運動期間最終日の一過性の運動の影響を取り除くため運動終了24時間後に実施した。採取した血液は遠心して血清を単離し、腓腹筋は懸濁してタンパクを抽出し、運動によるマイオカインの変動を網羅的に解析した。その結果、運動はマイオカインAが骨格筋および血中で増加することを立証した。また運動によるオートファジー基質の活性化がマイオカインAの発現を調節することを立証するため、オートファジー基質を筋特異的に増強および活性化したマウスを作成し、血液と腓腹筋のマイオカインAの発現を測定した。その結果、マイオカインAはオートファジー基質を増強すると骨格筋のmRNAとタンパクおよび血中のタンパクで増加することを確認した。これまでの先行研究を統合すると、マイオカインAは血管内皮細胞の機能を調節する可能性が期待されることから、次年度以降、血管内皮細胞に対するマイオカインAの役割を検討する。

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Committee Memberships 【 display / non-display 】

  • 2023.11
    -
    Now

      学術委員会委員

  • 2022.07
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    Now

      Associate Editor

  • 2021.09
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    Now

      評議員

  • 2021.01
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    Now

      Guest editor

  • 2019.02
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    2023.06

      Reviewing Editor

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