Rehabilitation of skeletal muscle of mice with Marfan syndrome: effect of eccentric exercise

• Grant number: 18/24946-4
• Support Opportunities: Regular Research Grants
• Duration: June 01, 2019 - November 30, 2021
• Field of knowledge: Health Sciences - Physiotherapy and Occupational Therapy
• Principal Investigator: Elen Haruka Miyabara
• Grantee: Elen Haruka Miyabara
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Marfan syndrome (SMF) is characterized by an autosomal dominant systemic disorder that affects connective tissue, since mutation occurs in the fibrillin-1 gene, with consequent alteration in the fibrillin-1 protein. Such protein is the main component of microfibrils present in the extracellular matrix of elastic and non-elastic connective tissues. Considering that: 1) the molecular mechanisms involved in the development of muscle fatigue, the reduction in muscle size, number of myofibers and in muscle strength of individuals with SMF are still not well understood and there is a lack of systematic studies characterizing muscle strength and the muscle fatigue resistance of these individuals; and that 2) SMF animal models have been developed to further investigate and better understand this syndrome; the best understanding of muscle contractile function in individuals with this syndrome is essential for the development of better muscle rehabilitation strategies for SMF patients. In addition, in view of 3) the beneficial effects of eccentric exercise on preventing muscle mass loss and / or improving muscle strength, the application of this exercise could be a viable physiotherapeutic rehabilitation strategy for SMF patients. Therefore, the present project aims to contribute to a better understanding of the skeletal muscle contractile function of SMF model mice (with mutation in fibrillin-1) and to investigate the effect of an eccentric (downhill running) exercise protocol on structural and functional rehabilitation of skeletal muscles from these animals. Macroscopic, histological, molecular and functional aspects of the soleus muscles from SMF and wild-type mice control and submitted to an eccentric exercise protocol will be evaluated (please verify the details in the project). (AU)