Sirtuins in the neuropathology of schizophrenia: the role against mitochondrial dysfunction during hypoxia

• Grant number: 15/25595-2
• Support type: Scholarships in Brazil - Master
• Effective date (Start): March 01, 2016
• Effective date (End): February 28, 2018
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal researcher: Tatiana Rosado Rosenstock
• Grantee: Luiz Felipe Souza e Silva
• Home Institution: Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP). Fundação Arnaldo Vieira de Carvalho. São Paulo , SP, Brazil

Abstract

The goal of this project is to investigate the role of sirtuins (SIRTs), specifically sirtuin 1, nuclear, and 3, mitochondrial, in mitochondrial dysfunction due to hypoxia in different animal and cellular models of Schizophrenia (SHZ): astrocytes exposed to CoCl2 and from spontaneous hypertensive rats, SHR. The significant value of this project is the fact that it is known that one of the main reasons leading to SHZ is fetal hypoxia; hypoxia is nominated as diminish in body flow oxygenation, or part of it, due to a decrease in oxygen tension. Namely mitochondria, which are close related to cellular metabolism and consume between 85 to 90% of O2 to ATP production, react to hypoxia changing its metabolism and dynamics. In fact, mitochondria are organelles able to modify constantly their shape and size, to mix their metabolites, as well as mitochondrial DNA copies (DNAmt) in an attempt to adapt to the energy demand. Therefore, the unbalance between all these processes, as occur during hypoxia, can affect negatively mitochondrial function and cellular proliferation, migration and differentiation, in addition to the formation of new synapses and neural viability. However, the relation between hypoxia versus SHZ is not clear yet. Recently, the theory that genetic and/or epigenetic modifications prejudice the prevalence and/or settle an augmentation of sensibility to external factor to SHZ, as hypoxia, is becoming the center of attention. Hence, the modulation of sirtuins, a lysine deacetylase which regulates transcription factor and proteins related to energy metabolism, would be a new therapeutic strategy against SHZ. (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)

SOUZA E SILVA, LUIZ FELIPE; BRITO, MARIANA DUTRA; CAMARGO YUZAWA, JESSICA MAYUMI; ROSENSTOCK, TATIANA ROSADO. Mitochondrial Dysfunction and Changes in High-Energy Compounds in Different Cellular Models Associated to Hypoxia: Implication to Schizophrenia. SCIENTIFIC REPORTS, v. 9, DEC 2 2019. (15/02041-1, 16/12039-7, 15/25595-2)

ARAUJO, BEATRIZ GRISOLIA; SOUZA E SILVA, LUIZ FELIPE; TORRESI, JORGE LUIZ DE BARROS; SIENA, AMANDA; VALERIO, BERENICE CATALDO OLIVEIRA; BRITO, MARIANA DUTRA; ROSENSTOCK, TATIANA ROSADO. Decreased Mitochondrial Function, Biogenesis, and Degradation in Peripheral Blood Mononuclear Cells from Amyotrophic Lateral Sclerosis Patients as a Potential Tool for Biomarker Research. Molecular Neurobiology, AUG 2020. (15/02041-1, 18/09084-6, 15/25595-2, 16/12039-7)