Elucidation of the molecular mechanism of skeletal muscle injury caused by serotonin agonists

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16609
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Tokyo Medical University
• Principal Investigator: Kawabata-Sakata Yukika 東京医科大学, 医学部, 助教 (80778473)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 骨格筋 / セロトニン / セロトニン症候群 / 横紋筋融解症

Outline of Final Research Achievements

To clarify the role of serotonin in skeletal muscle and the mechanism of skeletal muscle damage caused by administration of serotonin, we performed expression analysis of serotonin-related genes in mouse skeletal muscle and gene expression analysis in serotonin-administered C2C12 cells. As a result, it was suggested that serotonin production and metabolism differ depending on the muscle fiber type, and that they may be involved in muscle hypertrophy and/or muscle atrophy. In the analysis of cultured cells, gene expression such as energy metabolism-related genes decreased when added at a high concentration, and the formation of myotube was suppressed. The high concentration of serotonin administrated this time may be a model of C2C12 cells that cause skeletal muscle damage, we would like to use it to identify new therapeutic target molecules.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

セロトニン症候群は、セロトニン作動薬の服用により現れる副作用で、精神症状、神経筋症状、自律神経症状などが認められる疾患である。重篤な場合は、横紋筋融解症などの骨格筋障害を引き起こす。しかし、なぜセロトニンにより骨格筋が障害されるのか、さらには骨格筋におけるセロトニンの役割も不明な点が多い。本研究により、骨格筋におけるセロトニン産生や代謝は筋線維タイプごとに異なる可能性が示され、骨格筋でのセロトニンの具体的機能を解明する手がかりを掴んだ。また、セロトニン添加時の培養細胞を骨格筋が障害されるモデルとして使用することで、今後、治療標的分子の同定につながっていくと期待される。