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CHRONIC STRESS AND HIPPOCAMPAL NEUROGENESIS: ROLE OF PROBIOTICS AND LIPIDOMIC AND HORMONAL IMPLICATIONS

Grant number: 22/07245-8
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): October 01, 2022
Effective date (End): January 31, 2026
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Tatiana de Sousa da Cunha Uchiyama
Grantee:Raquel Cristina Melo Ferreira de Albuquerque Luz
Host Institution: Instituto de Ciência e Tecnologia (ICT). Universidade Federal de São Paulo (UNIFESP). Campus São José dos Campos. São José dos Campos , SP, Brazil
Associated research grant:17/17027-0 - Hormonal systems in renal and cardiovascular diseases: from cell biology to new physiological paradigms with advances for therapeutics, AP.TEM

Abstract

Stress is one of the most significant health problems in modern society and can be defined as an organic response to aversive stimuli or unknown situations capable of compromising homeostasis, which requires an adaptive response. Due to limitations inherent to research with human beings, animal models have been very useful in the study of the physiological mechanisms underlying the deleterious effects triggered by stress. Although it has been established that rodents adapt to repetitive stressful stimuli, this adaptation does not occur in methods of chronic unpredictable mild stress (CUMS), where alternating exposure to different stressor stimuli, for approximately 3 consecutive weeks, inducing continuous elevation of continuous levels of corticosterone and alteration of glycemic and lipid metabolism, observed up to 15 days after the application of the last stressor stimulus. Analyzing the mechanisms underlying the effects of stress on the brain, it was proposed that some components of the Renin-Angiotensin System (RAS) could be markers of stress and depression. In previous studies, we showed that CUMS induced an increase in circulating and hypothalamic levels of angiotensin II, and treatment with an angiotensin II blocker - AT1 (losartan) attenuated the development of these alterations. In addition, it has also been shown that stress alters the brain lipidome of rats, especially sphingomyelins, increasing the levels of ceramides in the hippocampus. Knowing that there is a close relationship between stress and the gut microbiota, the use of probiotics has been proposed as a therapeutic alternative in order to minimize stress and its harmful effects on different systems. Psychobiotics were first defined as the family of probiotics that, ingested in adequate concentrations, exert beneficial effects on mental health. Considering that: 1) stress has become a public health problem and that the number of individuals affected by complications resulting from chronic stress is increasing; 2) stress induces gastrointestinal dysbiosis with a negative impact on brain lipidome; 3) the lipidomic alteration results in a decrease in hippocampal function; 4) probiotics have a potential beneficial effect, favoring lipid balance and improving brain function, this study aims to evaluate the role of chronic administration of probiotics Lactobacillus rhamnosus and Lactobacillus reuteri, in changes in the gut-brain axis resulting from chronic stress , seeking in addition to a new therapeutic option for this disorder, the understanding of the pathways that are modulated by this resource.

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