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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 type:Scholarships in Brazil - Doctorate
Effective date (Start): January 01, 2021
Effective date (End): July 31, 2022
Field of knowledge:Health Sciences - Medicine - Psychiatry
Principal researcher:Tatiana Rosado Rosenstock
Grantee:Luiz Felipe Souza e Silva
Home 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)

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