The role of sirtuins on mitochondrial function and neurogenesis in different cellular models of hypoxia: relevance to schizophrenia genesis and progression

• Grant number: 18/13814-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): January 01, 2021
• Effective date (End): October 31, 2022
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Tatiana Rosado Rosenstock
• Grantee: Luiz Felipe Souza e Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Among all hypotheses related to Schizophrenia (SZ), we can highlight the neurodevelopment theory. According to it, environmental factors, such as hypoxia, could cause alterations and abnormalities in cellular machinery, including modifications in neural proliferation, migration and differentiation, in addition to changes in synapsis formation, which could lead to degenerative processes. However, the relationship between hypoxia and SZ is unknown. Considering that all the mechanisms aforementioned depends on energetic supply (ATP synthesis), the maintenance of mitochondrial metabolism is essential to keep cellular homeostasis. More recently, the theory that epigenetic alterations control the occurrence and/or determine the sensitivity to environmental factor (like hypoxia) is gaining attention. Concerning to this fact, the modulation of sirtuins (a class III lysine deacetylase), could be faced as a new therapeutic strategy. Therefore, the goal of this project is to evaluate the role of sirtuins on mitochondrial function and neurogenesis in different cellular models of hypoxia, neurons, co-culture (neurons and astrocytes), and neuroespheres from Wistar rats (control group) and SHR animals (a model of neonatal hypoxia) submitted to cobalt chloride treatment. Thus, investigate the role of SIRTs, which it is well-known to influence the regulation of transcription factors and proteins related to energetic metabolism, is crucial to understand the mechanisms that underlie the neural survival under low level of oxygen, and to the development of new therapeutic strategy against changes in neurodevelopmental processes. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SILVA, LUIZ FELIPE SOUZA E; SIENA, AMANDA; YUZAWA, JESSICA MAYUMI; DE BARROS TORRESI, JORGE LUIZ; ZIROLDO, ALAN; ROSENSTOCK, TATIANA ROSADO. Sirtuins Modulators Counteract Mitochondrial Dysfunction in Cellular Models of Hypoxia: Relevance to Schizophrenia. Neuroscience, v. 524, p. 16-pg., 2023-06-26. (15/02041-1, 15/25595-2, 18/13814-0, 19/17725-4)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SILVA, Luiz Felipe Souza e. Role of sirtuins on mitochondrial function and neurogenesis in different cellular models of hypoxia: relevance to the genesis and progression of schizophrenia.. 2022. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.