Sirtuins Modulators Counteract Mitochondrial Dysfunction in Cellular Models of Hypoxia: Relevance to Schizophrenia

Author(s)

Silva, Luiz Felipe Souza e ; Siena, Amanda ; Yuzawa, Jessica Mayumi ; de Barros Torresi, Jorge Luiz ; Ziroldo, Alan ; Rosenstock, Tatiana Rosado

• Document type: Journal article
• Source: Neuroscience; v. 524, p. 16-pg., 2023-06-26.

Abstract

(SZ) is a neurodevelopmental-associated disorder strongly related to environmental factors, such as hypoxia. Because there is no cure for SZ or any pharmacological approach that could revert hypoxia-induced cellular damages, we evaluated whether modulators of sirtuins could abrogate hypoxiainduced mitochondrial deregulation as a neuroprotective strategy. Firstly, astrocytes from control (Wistar) and Spontaneously Hypertensive Rats (SHR), a model of both SZ and neonatal hypoxia, were submitted to chemical hypoxia. Then, cells were exposed to different concentrations of Nicotinamide (NAM), Resveratrol (Resv), and Sirtinol (Sir) for 48hrs. Our data indicate that sirtuins modulation reduces cell death increasing the acetylation of histone 3. This outcome is related to the rescue of loss of mitochondrial membrane potential, changes in mitochondrial calcium buffering capacity, decreased O2 & DBLBOND;rad levels and increased expression of metabolic regulators (Nrf-1 and Nfe2l2) and mitochondrial content. Such findings are relevant not only for hypoxia-associated conditions, named pre-eclampsia but also for SZ since prenatal hypoxia is a relevant environmental factor related to this burdensome neuropsychiatric disorder.& COPY; 2023 IBRO. Published by Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 15/02041-1 - The role of lysine(K)-deacetylases on mitochondrial disorders's neuroprotection: perspectives of epigenetic therapy for amyotrophic lateral sclerosis and schizophrenia
• Grantee: Tatiana Rosado Rosenstock
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 15/25595-2 - Sirtuins in the neuropathology of schizophrenia: the role against mitochondrial dysfunction during hypoxia
• Grantee: Luiz Felipe Souza e Silva
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 18/13814-0 - The role of sirtuins on mitochondrial function and neurogenesis in different cellular models of hypoxia: relevance to schizophrenia genesis and progression
• Grantee: Luiz Felipe Souza e Silva
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/17725-4 - The role of mitochondrial degradation to cellular homeostasis: a study in patients stem cells (iPSC) with familial Amyotrophic Lateral Sclerosis
• Grantee: Thiago Garcia Varga
• Support Opportunities: Scholarships in Brazil - Scientific Initiation