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Effect of aerobic physical training on sympathetic nervous activity on skeletal muscle and tumoral tissue in Cancer cachexia

Grant number: 20/12279-3
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): February 01, 2021
Effective date (End): October 31, 2023
Field of knowledge:Biological Sciences - Physiology - Physiology of Effort
Principal researcher:Patricia Chakur Brum
Grantee:Gabriela Silva Borges
Home Institution: Escola de Educação Física e Esporte (EEFE). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Pathological changes in the autonomic nervous system have been proposed as sensitizing/potentiating factors in the Cancer continuum, contributing to its development, progression and aggressiveness. In fact, increases in Sympathetic Activity (SA) accelerate tumor progression in animal models of various types of Cancer, mainly through the activation of ²2-adrenergic receptors. It is also known that SA modulates the adipose and skeletal muscle tissue function, which have major morphofunctional and metabolic changes in cachexia, a syndrome common to some types of Cancer that is associated with increased mortality. Aerobic physical training (AFT) has been considered a potential complementary therapy for Cancer. Among its effects, there is a reduction in tumor volume associated with better perfusion and immune response in the tumor microenvironment and an improvement in contractile function with increased survival. In addition, a classic effect of AFT is the reduction of sympathetic hyperactivity and improvement in dysautonomy in different chronic diseases. In view of the role of SA in Cancer and the effects of AFT on SA and Cancer, we hypothesise that AFT may contribute to the reduction of tumor progression and improve cachexia via SA modulation. Our aim is to investigate the effects of AFT on muscle function and tumor volume in a model of cachexia induced by colon carcinoma (CT26) in mice and their relationship with sympathetic innervation, density of ²2-adrenergic receptors and their signaling pathways in both tissues. (AU)