Effect of aerobic physical training on sympathetic nervous Activity on skeletal muscle and tumoral tissue in cancer cachexia

Author(s)

Gabriela Silva Borges

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Escola de Educação Física e Esportes (EEFE/BT)
• Defense date: 2024-11-12

Examining board members

Patricia Chakur Brum; Anamaria Aranha Camargo; João Agostinho Machado Neto; Edilamar Menezes de Oliveira

• Advisor: Patricia Chakur Brum

Abstract

Dysautonomia has been related to cancer development, progression, and aggressiveness. Increased sympathetic nervous activity (SA) accelerate tumor growth in animal models of various types of tumor, modulating adipose and skeletal muscle tissue functions, which have major morphofunctional and metabolic changes in cachexia, a syndrome prevalent to some types of cancer and associated with increased mortality. Aerobic physical exercise training (AET) has been considered a potential complementary therapy for cancer. Among its effects, the most important are prevention, and after cancer development, increase in survival rates. Also, a classic effect of AET is the reduction of sympathetic hyperactivity and improvement in dysautonomia in different chronic diseases. Considering the role of SA in cancer and the effects of AFT on SA and cancer, the hypothesis of this research is that AET may contribute to the reduction of tumor progression and improve muscle and muscular function loss via SA modulation. The main goal is to investigate the effects of AET on muscle function and tumor volume in a model of cancer induced by colon carcinoma (CT26) in mice and their relationship with adrenergic signaling pathways in both tissues. The results indicate that AET is capable of attenuate tumor growth and increase survival rates without changing classic intracellular signaling of adrenergic activation on both tumor and skeletal muscle. No differences were found in body mass, tumor volume and tissue mass at the end of the protocol in animals treated with 2-adrenergic antagonist (ICI). However, we observed increased expression of protein kinase A (PKA) and the phosphorylated form of CREB, a target of PKA in animals treated with ICI. AET was able to attenuate tumor growth and increase survival rate in our model, as well as prevent the loss of functional capacity of animals with cancer. We did not observe differences in mRNA expression for the 2-adrenergic receptor, as well as in the classical intracellular signaling pathway of adrenergic activation in tumor tissue and skeletal muscle between the groups of trained and untrained animals. It is possible that adrenergic signaling related to immune system organs is affected in cancer, since these organs hypertrophied and the behavior of lymphocytes in the tumor microenvironment is influenced by the training state (AU)

• FAPESP's process: 20/12279-3 - Effect of aerobic physical training on sympathetic nervous activity on skeletal muscle and tumoral tissue in Cancer cachexia
• Grantee: Gabriela Silva Borges
• Support Opportunities: Scholarships in Brazil - Doctorate