Development of an innovative adjuvant therapy with combination of neuromuscular electrical stimulation and eccentric contraction for improvement of muscle strength in arthritis disorders

• Project/Area Number: 26702021
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Rehabilitation science/Welfare engineering
• Research Institution: Sapporo Medical University
• Principal Investigator: Yamada Takashi 札幌医科大学, 保健医療学部, 准教授 (50583176)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥19,760,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥4,560,000); Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2014: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
• Keywords: 介護予防 / 関節疾患 / 筋力低下 / 神経筋電気刺激 / 酸化ストレス / 筋力 / 伸張性収縮

Outline of Final Research Achievements

We investigated the effects of neuromuscular electrical stimulation (ES) training with eccentric contraction (ECC) on skeletal muscle dysfunction in adjuvant-induced arthritis (AIA) rat. AIA was induced by an injection of complete Freund’s adjuvant. ES was applied every other day for three weeks. There was a reduction in specific force production in skinned fibers from medial gastrocnemius (MG) muscles from AIA rats, which was accompanied by the aggregation of actin. Moreover, the protein expressions of the pro-oxidative enzymes NADPH oxidase, neuronal nitric oxide synthase, and p62 were increased in AIA EDL muscles. These deleterious changes were prevented by ES training. The present data suggest that NMES training prevents AIA-induced skeletal muscle weakness presumably by counteracting the formation of actin aggregates. Thus, ES training with ECC can be effective in treatment of muscle dysfunction seen in patients with arthritis disorders.

Research Products

• [Int'l Joint Research] Karolinska Institute(Sweden)
• [Int'l Joint Research]
• [Int'l Joint Research] カロリンスカ研究所(スウェーデン)
• [Journal Article] 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 (2017)
  • Author(s): 檜森弘一，舘林大介，大山友加，青木達彦，山田崇史
  • Journal Title: 日本基礎理学療法学雑誌 Volume: 印刷中
  • NAID: 130007490548
  • Peer Reviewed
• [Journal Article] Role of calpain in eccentric contraction-induced proteolysis of Ca2+-regulation proteins and force depression in rat fast-twitch skeletal muscle (2017)
  • Author(s): Kanzaki, K., Watanabe, D., Kuratani, M., Yamada, T., Matsunaga, S., Wada, M.
  • Journal Title: J Appl Physiol Volume: 122 Issue: 2 Pages: 396-407
  • DOI: 10.1152/japplphysiol.00270.2016
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Superoxide dismutase/catalase mimetic EUK-134 prevents diaphragm muscle weakness in monocrotalin-induced pulmonary hypertension (2017)
  • Author(s): Himori K, Abe M, Tatebayashi D, Lee J, Westerblad H, Lanner JT, Yamada T.
  • Journal Title: PLoS One Volume: 12 Issue: 2 Pages: e0169146-e0169146
  • DOI: 10.1371/journal.pone.0169146
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The role of reactive oxygen species in β-adrenergic signaling in cardiomyocytes from mice with the metabolic syndrome (2016)
  • Author(s): Llano-Diez M, Sinclair J, Yamada T, Zong M, Fauconnier J, Zhang SJ, Katz A, Jardemark K, Westerblad H, Andersson DC, Lanner JT.
  • Journal Title: PLoS One Volume: 11 Issue: 12 Pages: e0167090-e0167090
  • DOI: 10.1371/journal.pone.0167090
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 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 (2016)
  • Author(s): 舘林大介，檜森弘一，阿部真佐美，李宰植，山田崇史
  • Journal Title: 日本基礎理学療法学雑誌 Volume: 19 Pages: 55-64
  • NAID: 130007492843
  • Peer Reviewed
• [Journal Article] 熱刺激負荷がアジュバント関節炎ラットの長趾伸筋における収縮機能に及ぼす影響 (2016)
  • Author(s): 7.李宰植，阿部真佐美，舘林大介，檜森弘一，山田崇史
  • Journal Title: 日本基礎理学療法学雑誌 Volume: 19 Pages: 39-47
  • NAID: 130007491172
  • Peer Reviewed
• [Journal Article] Free radical signaling behind the muscle weakness associated with rheumatoid arthritis (2016)
  • Author(s): Yamada T and Lanner JT.
  • Journal Title: EMJ Rheumatology Volume: 3.1 Pages: 87-89
  • Int'l Joint Research
• [Journal Article] ROS/RNS and contractile function in skeletal muscle during fatigue and recovery (2016)
  • Author(s): 2.Cheng AJ, Yamada T, Rassier DE, Andersson DC, Westerblad H, Lanner JT.
  • Journal Title: J. Physiol. Volume: 594 Issue: 18 Pages: 5149-5160
  • DOI: 10.1113/jp270650
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Muscle dysfunction associated with adjuvant induced-arthritis is prevented by antioxidant treatment (2015)
  • Author(s): Yamada, T., Abe, M., Lee, J., Tatebayashi, D., Himori, K., Kanzaki, K., Wada, M., Bruton, JD., Westerblad, H. and Lanner, JT.
  • Journal Title: Skeletal Muscle Volume: 5 Issue: 1 Pages: 20-20
  • DOI: 10.1186/s13395-015-0045-7
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Response of heat shock protein 72 to repeated bouts of hyperthermia in rat skeletal muscle (2015)
  • Author(s): Lee, J., Himori, K., Tatebayashi, D., Abe, M. and Yamada, T.
  • Journal Title: Physiol. Res. Volume: 64 Pages: 935-938
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 関節リウマチに伴う筋弱化のメカニズム (2015)
  • Author(s): 山田崇史
  • Journal Title: 理学療法学 Volume: 42 Pages: 819-820
  • NAID: 130005119650
• [Journal Article] Nitrosative modifications of the Ca2+ release complex and actin underlie arthritis-induced muscle weakness (2014)
  • Author(s): Yamada, T., Fedotovskaya, O., Cheng, AJ., Cornachione, AS., Minozzo, FC., Aulin, C., Friden, C., Turesson, C., Andersson, DC., Glenmark, B., Lundberg, IE., Rassier, DE., Westerblad, H., Lanner, JT.
  • Journal Title: Ann. Rheum. Dis. Volume: in press Issue: 10 Pages: 1907-1914
  • DOI: 10.1136/annrheumdis-2013-205007
  • Peer Reviewed / Open Access
• [Presentation] プレコンディショニングは伸張性収縮後の酸化ストレスを防止し機能回復を促進する (2017)
  • Author(s): 山田遼太郎，檜森弘一，舘林大介，山田崇史
  • Organizer: 第5回骨格筋生物学研究会
  • Place of Presentation: 東京大学，東京都
  • Year and Date: 2017-03-03
• [Presentation] 伸張性収縮トレーニングはアジュバント関節炎ラットの筋機能とオートファジー動態を改善する (2017)
  • Author(s): 檜森弘一，舘林大介，山田遼太郎，山田崇史
  • Organizer: 第5回骨格筋生物学研究会
  • Place of Presentation: 東京大学，東京都
  • Year and Date: 2017-03-03
• [Presentation] 伸張性収縮トレーニングがcolon 26癌モデルマウスの筋萎縮に及ぼす影響 (2017)
  • Author(s): 舘林大介，檜森弘一，山田遼太郎，山田崇史
  • Organizer: 第5回骨格筋生物学研究会
  • Place of Presentation: 東京大学，東京都
  • Year and Date: 2017-03-03
• [Presentation] 神経-筋電気刺激トレーニングは重症疾患ミオパチーモデルラットにおける筋弱化を改善する (2017)
  • Author(s): 山田崇史，山田遼太郎，檜森弘一，舘林大介，升田好樹，今井富裕
  • Organizer: 第5回骨格筋生物学研究会
  • Place of Presentation: 東京大学，東京都
  • Year and Date: 2017-03-03
• [Presentation] 神経-筋電気刺激及びグルタミン投与の併用が癌性筋萎縮に及ぼす影響 (2016)
  • Author(s): 舘林大介，檜森弘一，山田崇史
  • Organizer: 第71回日本体力医学会大会
  • Place of Presentation: いわて県民情報交流センター・盛岡地域交流センター市民文化ホール，盛岡市
  • Year and Date: 2016-09-23
• [Presentation] 神経－筋電気刺激による筋の限界肥大率は負荷強度に規定される (2016)
  • Author(s): 檜森弘一，舘林大介，大山友加，青木達彦，山田崇史
  • Organizer: 第71回日本体力医学会大会
  • Place of Presentation: いわて県民情報交流センター・盛岡地域交流センター市民文化ホール，盛岡市
  • Year and Date: 2016-09-23
• [Presentation] Effects of electrical stimulation training on muscle atrophy and glucocorticoid signaling in colon 26 tumor bearing mice (2016)
  • Author(s): Tatebayashi D, Himori K, Abe M, Lee J, Yamada T
  • Organizer: 45th European Muscle Conference
  • Place of Presentation: Montpellier, France
  • Year and Date: 2016-09-02
  • Int'l Joint Research
• [Presentation] Neuromuscular electrical stimulation prevents skeletal muscle dysfunction in adjuvant-induced arthritis rat (2016)
  • Author(s): Himori K, Abe M, Tatebayashi D, Lee J, Yamada T
  • Organizer: 45th European Muscle Conference
  • Place of Presentation: Montpellier, France
  • Year and Date: 2016-09-02
  • Int'l Joint Research
• [Presentation] Pulmonary hypertension-induced diaphragm muscle weakness was prevented by treatment with antioxidant (2016)
  • Author(s): Yamada T, Himori K, Abe M, Tatebayashi D, Lee J, Westerblad H, Lanner JT
  • Organizer: 45th European Muscle Conference
  • Place of Presentation: Montpellier, France
  • Year and Date: 2016-09-02
  • Int'l Joint Research
• [Presentation] Contribution of calstabin1 binding to impaired ryanodine receptor with prolonged low-frequency force depression (2016)
  • Author(s): Aibara, C., Watanabe, D., Yamada, T., Wada, M.
  • Organizer: The 93rd Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: 札幌コンベンションセンター，札幌市
  • Year and Date: 2016-03-22
• [Presentation] Antioxidant treatment prevents pulmonary hypertension-induced diaphragm dysfunction (2016)
  • Author(s): Himori K, Abe M, Tatebayashi D, Lee J, Yamada T.
  • Organizer: The 93rd Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: 札幌コンベンションセンター，札幌市
  • Year and Date: 2016-03-22
• [Presentation] Effects of electrical stimulation training on muscle atrophy in a mouse model of cancer cachexia (2016)
  • Author(s): Tatebayashi D, Himori K, Abe M, Lee J, Yamada T.
  • Organizer: The 93rd Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: 札幌コンベンションセンター，札幌市
  • Year and Date: 2016-03-22
• [Presentation] 神経-筋電気刺激トレーニングはアジュバント関節炎ラットにおける筋弱化を防止する (2016)
  • Author(s): 山田崇史
  • Organizer: 第4回骨格筋生物学研究会
  • Place of Presentation: 松本大学，松本市
  • Year and Date: 2016-03-04
• [Presentation] 肺高血圧症ラット横隔膜の収縮機能低下に対する抗酸化剤投与の効果 (2016)
  • Author(s): 檜森弘一，阿部真佐美，舘林大介，李宰植，山田崇史
  • Organizer: 第4回骨格筋生物学研究会
  • Place of Presentation: 松本大学，松本市
  • Year and Date: 2016-03-04
• [Presentation] 癌性カへキシアに伴う筋量低下は神経-筋電気刺激により防止されるか？ (2016)
  • Author(s): 舘林大介，檜森弘一，阿部真佐美，李宰植，山田崇史．
  • Organizer: 第4回骨格筋生物学研究会
  • Place of Presentation: 松本大学，松本市
  • Year and Date: 2016-03-04
• [Presentation] 神経―筋電気刺激トレーニング誘発性の筋肥大における力積の役割 (2015)
  • Author(s): 山田崇史，大山友加，青木達彦，舘林大介，檜森弘一．
  • Organizer: 第2回日本基礎理学療法学会学術大会および日本基礎理学療法学会第20回学術大会合同学会
  • Place of Presentation: 神奈川県立保健福祉大学，横須賀市
  • Year and Date: 2015-11-14
• [Presentation] 神経-筋電気刺激が癌性カヘキシアに伴う筋量低下に及ぼす影響． (2015)
  • Author(s): 舘林大介，檜森弘一，阿部真佐美，李宰植，山田崇史．
  • Organizer: 第23回日本物理療法学会
  • Place of Presentation: 神戸学院大学有瀬キャンパス，明石市
  • Year and Date: 2015-10-24
• [Presentation] アジュバント関節炎ラットの長趾伸筋における収縮機能の低下は神経―筋電気刺激により防止されるか？ ―酸化還元動態に着目して―． (2015)
  • Author(s): 檜森弘一，舘林大介，李宰植，阿部真佐美，山田崇史．
  • Organizer: 第23回日本物理療法学会
  • Place of Presentation: 神戸学院大学有瀬キャンパス，明石市
  • Year and Date: 2015-10-24
• [Presentation] Antioxidant treatment prevents skeletal muscle dysfunction in adjuvant-induced arthritis rats (2015)
  • Author(s): Yamada T, Abe M, Lee J, Tatebayashi D, Himori K, Kanzaki K, Wada M, Bruton JD, Westerblad H. and Lanner JT.
  • Organizer: 44th European Muscle Conference.
  • Place of Presentation: Warsaw, Poland.
  • Year and Date: 2015-09-21
  • Int'l Joint Research
• [Presentation] 抗酸化剤EUK-134は肺高血圧症ラットの横隔膜における収縮機能低下を抑制する (2015)
  • Author(s): 阿部真佐美，李宰植，舘林大介，檜森弘一，山田崇史．
  • Organizer: 第70回日本体力医学会大会
  • Place of Presentation: 和歌山県民文化会館，和歌山市
  • Year and Date: 2015-09-18
• [Presentation] 癌性カヘキシアにおける骨格筋のグルタミン合成酵素の発現動態 (2015)
  • Author(s): 舘林大介，檜森弘一，阿部真佐美，李宰植，山田崇史．
  • Organizer: 第70回日本体力医学会大会
  • Place of Presentation: 和歌山県民文化会館，和歌山市
  • Year and Date: 2015-09-18
• [Presentation] 神経―筋電気刺激がアジュバント関節炎ラットの長趾伸筋における収縮機能に及ぼす影響 (2015)
  • Author(s): 檜森弘一，舘林大介，李宰植，阿部真佐美，山田崇史．
  • Organizer: 第70回日本体力医学会大会
  • Place of Presentation: 和歌山県民文化会館，和歌山市
  • Year and Date: 2015-09-18
• [Presentation] 抗酸化剤の投与はアジュバント関節炎ラットにおける筋機能低下を防止する (2015)
  • Author(s): 山田崇史，阿部真佐美，李宰植，舘林大介，檜森弘一，神崎圭太，和田正信， Bruton JD，Westerblad H，Lanner JT．
  • Organizer: 第1回日本筋学会
  • Place of Presentation: 国立研究開発法人国立精神・神経医療研究センター，東京都小平市
  • Year and Date: 2015-08-08
• [Presentation] 抗酸化剤はアジュバント関節炎に伴う筋弱化を防止するか？ (2015)
  • Author(s): 山田崇史
  • Organizer: 第3回骨格筋生物学研究会
  • Place of Presentation: 東北大学，仙台市
  • Year and Date: 2015-03-06 – 2015-03-08
• [Presentation] アジュバント関節炎ラットの長趾伸筋における筋弱化のメカニズム -アクチンの酸化的修飾によるアクトミオシンATPase活性の低下- (2014)
  • Author(s): 山田崇史，阿部真佐美，李宰植，舘林大介，檜森弘一
  • Organizer: 第1回日本基礎理学療法学会学術大会および日本基礎理学療法学会第4回学術大会合同学会
  • Place of Presentation: 名古屋学院大学，名古屋市
  • Year and Date: 2014-11-15 – 2014-11-16
• [Presentation] 熱刺激が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 (2014)
  • Author(s): 阿部真佐美，李宰植，舘林大介，檜森弘一，山田崇史
  • Organizer: 第69回日本体力医学会大会
  • Place of Presentation: 長崎大学，長崎市
  • Year and Date: 2014-09-19 – 2014-09-21
• [Presentation] 熱刺激負荷がアジュバント関節炎ラットの長趾伸筋における収縮機能に及ぼす影響 (2014)
  • Author(s): 李宰植，阿部真佐美，舘林大介，檜森弘一，山田崇史
  • Organizer: 第69回日本体力医学会大会
  • Place of Presentation: 長崎大学，長崎市
  • Year and Date: 2014-09-19 – 2014-09-21
• [Presentation] 自発運動を課した2型糖尿病ラットにおける運動パフォーマンスと筋組成，筋酵素活性について (2014)
  • Author(s): 高田義弘，竹下大輔，花岡智子，奥田俊詞，鷲尾弘枝，石見恵子，保井俊英，今北英高，峯松亮，星野聡子，山田崇史，和気秀文，中村友浩，岡田修一，平川和文，中谷昭，坂田進
  • Organizer: 第69回日本体力医学会大会
  • Place of Presentation: 長崎大学，長崎市
  • Year and Date: 2014-09-19 – 2014-09-21
• [Presentation] Effects of heat stress on contractile function in the diaphragm from rat with pulmonary hypertension (2014)
  • Author(s): Abe, M., Lee, J., Tatebayashi, D., Himori, K., Yamada, T.
  • Organizer: 43th European Muscle Conference
  • Place of Presentation: Salzburg, Austria
  • Year and Date: 2014-09-10 – 2014-09-14
• [Presentation] Intermittent heat stress fails to ameliorate contractile dysfunction in extensor digitorum longus muscle from adjuvant-induced arthritis rats (2014)
  • Author(s): Lee, J., Abe, M., Tatebayashi, D., Himori, K., Yamada, T.
  • Organizer: 43th European Muscle Conference
  • Place of Presentation: Salzburg, Austria
  • Year and Date: 2014-09-10 – 2014-09-14
• [Presentation] Impaired myosin ATPase activity due to actin oxidation underlies skeletal muscle dysfunction in adjuvant-induced arthritis rat (2014)
  • Author(s): Yamada, T., Abe, M., Lee, J., Tatebayashi, D., Himori, K., Chikazoe, S., Hirota, K.
  • Organizer: 43th European Muscle Conference
  • Place of Presentation: Salzburg, Austria
  • Year and Date: 2014-09-10 – 2014-09-14