Analysis of serum biomarkers of neuroprotection and aging (sirtuin 3 and klotho) in mild amnestic cognitive impairment and APPSWE/PS1DE9 mice, after physical exercise of moderate intensity

• Grant number: 19/27833-9
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2021
• End date: March 31, 2024
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Paulo Henrique Ferreira Bertolucci
• Grantee: Paulo Henrique Ferreira Bertolucci
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Arlete Rita Penitente Barcelos ; Carlos André Freitas dos Santos ; Fernando Morgadinho Santos Coelho ; Raul Cavalcante Maranhao ; Ricardo Mario Arida ; SANDRO LUIZ DE ANDRADE MATAS
• Associated scholarship(s): 23/03639-4 - ANALYSIS OF SERUM BIOMARKERS OF NEUROPROTECTION AND AGING (SIRTUIN 3 AND KLOTHO) IN PATIENTS WITH MILD COGNITIVE IMPAIRMENT AMNESTIC AND APPSWE/PS1DE9 MICE, BEFORE AND AFTER MODERATE INTENSITY PHYSICAL EXERCISE, BP.TT; 22/09190-6 - ANALYSIS OF SERUM BIOMARKERS OF NEUROPROTECTION AND AGING (SIRTUÍNA 3 AND KLOTHO) IN MILD AMNESTIC COGNITIVE IMPAIRMENT AND APPSWE/PS1DE9 MOUSE, AFTER PHYSICAL EXERCISE OF MODERATE INTENSITY, BP.TT

Abstract

The objective of this study is to analyze serum and cerebrospinal fluid biomarkers in individuals with mild amnestic cognitive impairment (CCL) and serum biomarkers and brain histological analysis in female APPSWE / PS1DE9 mice in the CCL phase, to better understand the mechanisms of this phase of dementia and seek new possibilities in terms of non-pharmacological treatment. At least 30 patients diagnosed with amnestic CCL (who are not engaged in regular exercise or sedentary patients) and 30 control patients with the same characteristics will be selected, monitored for moderate intensity exercise, 150 minutes / week (within 3, 6, 9 and 12 months for each patient). Patients in the amnestic CCL groups and the control group will be considered responders if they maintain the Montreal Cognitive Assessment (MoCA) scores d 24 points after one year, with improved executive function, or no behavioral deterioration based on reports from caregivers. These same groups will be evaluated for serum biomarkers sirtuin 3 (SIRT3) and klotho, inflammatory biomarkers (IL-6, IL-1² and TNF-±) and of cerebrospinal fluid biomarkers (levels of Tau proteins-T, P-tau and A²-42), before and after physical exercise of moderate intensity monitored, and will be compared with a control negative group. It will be considered as positive response: Montreal Cognitive Assessment (MoCA) d 24 points after one year, with improvement in executive function, and stable or improved behavior, based on reports from caregivers. In this study will also be used 100 female APPSWE / PS1DE9 mice and their respective controls, divided into groups: 1) Sedentary CCL; 2) Sedentary controls; 3) Sedentary CCL and submitted to the test of spatial memory, cognition and executive function; 4) Sedentary controls and subjected to the test of spatial memory, cognition and executive function; 5) Sedentary CCL submitted to the context fear test; 6) Sedentary control submitted to the context fear test; 7) CCL trained; 8) Trained controls; 9) CCL trained and subjected to the test of spatial memory, cognition and executive function; 10) Control trained and subjected 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 undergo to an aerobic training program for four weeks. APPSWE / PS1DE9 mice will be evaluated for 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 context fear conditioning task. In these animals will also be evaluated serum biomarkers SIRT3 and klotho, inflammatory (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. It is expected that the moderate intensity exercise will induce a differentiated response to the evolution of amnestic CCL, both in patients and in the experimental model APPSWE / PS1DE9, increasing the expression of neuroprotection biomarkers, improving the behavioral, cognitive and executive function and managing to slow the evolution of the pathogenesis of amnestic CCL and Alzheimer's disease. (AU)