THE ROLE OF TUMOR NECROSIS FACTOR RECEPTOR 1 IN THE EFFECTS OF PHYSICAL EXERCISE AND ITS POSSIBLE IMPLICATIONS IN NEUROINFLAMMATION

• Grant number: 24/10817-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2025
• End date: May 31, 2028
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Elisa Mitiko Kawamoto Iwashe
• Grantee: Thiago Amorim de Souza Lima
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/06009-6 - Neuroplasticity -induced by challenge Na, K-ATPase, Klotho, glutamate, and neuroinflammation signaling cascades to reveal new therapeutic targets for aging and neurodegenerative diseases, AP.TEM

Abstract

Physical exercise is utilized as a non-pharmacological strategy to promote various benefits, such as improved cognition and reduced neuroinflammation. Animals subjected to physical exercise and then challenged with lipopolysaccharide (LPS), known to induce neuroinflammation, show attenuated negative effects of LPS. However, the mechanism by which this attenuation of LPS effects occurs is not well understood. Tumor necrosis factor (TNF-±) is a cytokine that regulates synaptic plasticity processes through the activation of its type 1 receptor (TNFR1), being directly linked to learning and memory processes. In immune challenge situations, the activation of TNFR1 can deregulate synaptic plasticity and induce impairments in learning and memory functions. Due to its dual role inside and outside of immune challenge, it is possible that TNFR1 signaling is linked to the mechanism of exercise-induced attenuation of neuroinflammation. For this, wild-type and TNFR1 knockout animals will be used, separated into eight groups: (A) WT sedentary; (B) WT exercise; (C) KO sedentary; and (D) KO exercise. They will undergo voluntary physical exercise, followed by administration of saline or LPS. After immune challenge induction, working memory, inflammatory profile (GFAP, COX2, and iNOS) by Western Blot, pro-inflammatory (TNF-±, IL-1²) and anti-inflammatory (IL-10) cytokines, and BDNF by ELISA kit, synaptic plasticity by electrophysiology, and activation of the transcription factor NF-ºB by EMSA will be evaluated.