ANALYSIS OF SERUM NEUROPROTECTION AND AGING BIOMARKERS (SIRTUIN 3 AND KLOTHO) IN APPSWE/PS1DE9 MICE, BEFORE AND AFTER MODERATE INTENSITY PHYSICAL EXERCISE

• Grant number: 22/08671-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): August 01, 2022
• Effective date (End): July 31, 2023
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Paulo Henrique Ferreira Bertolucci
• Grantee: Sthefanie Ferreira de Souza Dias Otaviano
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

This study aims to analyze serum biomarkers and brain histological analysis in female APPSWE/PS1DE9 mice, in the Mild Cognitive Impairment (MCI) phase, after moderate-intensity physical exercise. In this study, at least 120 female APPSWE/PS1DE9 mice and their respective controls will be used, divided into groups: 1) sedentary MCC; 2) Sedentary controls; 3) sedentary MCI and submitted to spatial memory, cognition and executive function tests; 4) Controls sedentary and submitted to the test of spatial memory, cognition and executive function; 5) sedentary MCC submitted to the context fear test; 6) Sedentary control submitted to the fear of context test; 7) Trained CCL; 8) Trained controls; 9) MCI trained and submitted to spatial memory, cognition and executive function tests; 10) Control trained and submitted to the test of spatial memory, cognition and executive function; 11) CCL trained and subjected to the context fear test; 12) Control trained and subjected to the context fear test. The animals in the exercise group will be submitted to an aerobic training program for four weeks. APPSWE/PS1DE9 mice will be evaluated locomotor and exploratory activity by the open field test, long-term memory (LTM) by the object recognition test and the learning and memory processes by the fear conditioning task to the context. In these animals, serum biomarkers SIRT3 and klotho, serum inflammatory biomarkers (IL-6, IL-1² and TNF-±) and immunohistochemistry for A²-42 biomarker and visualization of A²-42 plaque deposition in the cortex and hippocampus regions will also be evaluated. . It is expected that moderate-intensity physical exercise will determine a differentiated response regarding the evolution of amnestic MCI, in the APPSWE/PS1DE9 experimental model, increasing the expression of neuroprotection biomarkers, observing improvement in behavioral, cognitive and executive function, managing to delay the evolution of the pathogenesis of amnestic MCI and Alzheimer's disease.