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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: Neuroscience; v. 524, p. 16-pg., 2023-06-26.

Resumo

(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)

• Processo FAPESP: 15/02041-1 - O papel das lisinas(K)-deacetilases para a neuroproteção de desordens mitocondriais: perspectivas de terapia epigenética para a esclerose lateral amiotrófica e esquizofrenia
• Beneficiário: Tatiana Rosado Rosenstock
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 15/25595-2 - Sirtuínas na neuropatologia da esquizofrenia: implicação contra a disfunção mitocondrial na hipóxia
• Beneficiário: Luiz Felipe Souza e Silva
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 18/13814-0 - Papel das sirtúinas sobre a função mitocondrial e a neurogênese em diferentes modelos celulares de hipóxia: relevância para gênese e progressão da esquizofrenia
• Beneficiário: Luiz Felipe Souza e Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 19/17725-4 - O papel da degradação mitocondrial para a homeostase celular: um estudo em células tronco (iPSC) de pacientes com Esclerose Lateral Amiotrófica familiar
• Beneficiário: Thiago Garcia Varga
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica