Behavioral assessment and global profile of proteins and cortical and hippocampal markers of autophagy and Alzheimer's during aging in male and female mice subjected to protein restriction or gestational stress.

• Grant number: 24/06071-1
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2024
• End date: October 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Patrícia Aline Boer
• Grantee: Patrícia Aline Boer
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Jose Antonio Rocha Gontijo

Abstract

Aging is defined as progressive functional decline promoting a decrease in reproductive capacity, the emergence of diseases and an increase in the mortality rate. The prevalence of chronic diseases modulated by environmental factors has influenced the healthy aging and longevity of the population. The DOHaD (Developmental Origins of Health and Disease) area investigates the effects of adverse events during the prenatal period, such as nutritional and psychosocial stress, which can lead to adaptations in the fetus, predisposing the individual to metabolic, endocrine and behavioral and neuropsychiatrics disorders. Although these two types of stress can cause similar consequences, there are no comparative experimental studies of these two models, investigating the aging process in males and females. Thus, this project aims to comparatively evaluate the behavior, the global profile of cortical and hippocampal proteins and the process of autophagy and the development of Alzheimer's disease (AD), in male and female mice subjected to protein restriction or chronic gestational stress, in 12th and 18th month of life. C57 and CAG-RFP-EGFP-LC3, C57BL/6-Tg (CAG-RFP/GFP/Map1lc3b)1HILL/JCAG-RFP-EGFP-LC3 transgenic mice will be used (Jackson Laboratory - Mouse Strain DATA SHEET - 027139 - USA) pregnant mice will be divided into two groups: 1) will receive an NP (17% protein) or LP diet (low-protein, 6% protein); 2) subjected to the control environment (C) or to the moderate chronic stress protocol (St, 6th to 18th gestational day). The maternal behavior will be evaluated. In the 12th and 18th month of life, males and females of the offspring will be subjected to behavioral tests and their cortex and hippocampus tissues will be processed for proteomic analysis, quantification of autophagy and AD markers. We hypothesized to find proteins whose regulation is altered, differently in the two models, and which may be related to the behavioral changes observed. The changes may favor the early appearance of failures in the autophagy process and the consequent appearance of deposits characteristic of AD. If our working hypothesis is confirmed, the mechanisms and pathways related to such effects will be an important line of investigation, raising new and relevant questions for the area. (AU)