Association between melatonin and low-intensity aerobic exercise in the utrophin increase in the cardiac muscle of mdx mice

• Grant number: 21/08197-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2021
• End date: September 30, 2022
• Field of knowledge: Health Sciences - Physiotherapy and Occupational Therapy
• Principal Investigator: Anabelle Silva Cornachione
• Grantee: Júlia Furlan Chinelatto
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Duchenne Muscular Dystrophy (DMD) is the most common and severe muscular dystrophy that affects about 21.4 in 100,000 boys born alive. It occurs due to the absence of dystrophin protein, resulting in progressive loss of muscle tissue, muscle weakness, and cardiomyopathy. Since there is no cure for DMD, treatments involving physical and pharmacological therapies are constantly explored, and low-intensity aerobic exercises have been improving the capacity of the dystrophic cardiac muscle, although they can increase the degenerative process due to the production of ROS (reactive oxygen species). In order to contain this production, it is common to use drugs, such as melatonin, a hormone that leads to an increase in utrophin protein, a homolog of dystrophin that has great importance in cardiomyopathies of DMD patients. However, few studies have demonstrated the benefits of the association between low-intensity aerobic exercise and melatonin in the cardiac muscle. Thus, the objective of this project is to analyze the content of utrophin and nitrotyrosine (ROS marker) in the cardiac muscle of mdx mice after low-intensity aerobic training associated with melatonin. For this purpose, 24 mdx animals will be randomized into four groups: (1) sedentary (mdxS); (2) melatonin (mdxM); (3) trained with melatonin (mdx trim) and (4) trained (mdxTR). After the procedures, the animals will be euthanized and their hearts excised for analysis of utrophin and nitrotyrosine through Western Blotting and Immunofluorescence. We expect to verify a positive adaptation of the dystrophic cardiac tissue, with an increase in utrophin content and a decrease in nitrotyrosine due to the low-intensity aerobic training associated with melatonin. (AU)