• E SilvaLuiz Felipe SouzaLFSDepartment of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil., Amanda Siena, YuzawaJessica MayumiJMDepartment of Physiological Science, Santa Casa de São Paulo School of Medical Science, São Paulo, Brazil., TorresiJorge Luiz de BarrosJLBDepartment of Physiological Science, Santa Casa de São Paulo School of Medical Science, São Paulo, Brazil., Alan Ziroldo, and RosenstockTatiana RosadoTRDepartment of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil; Dept. of Bioscience, In-vitro Neuroscience, Sygnature Discovery, Nottingham, United Kingdom. Electronic address: tatirosenst.
• Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil.
• Neuroscience. 2023 Aug 1; 524: 269284269-284.

AbstractSchizophrenia (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 hypoxia-induced 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-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.Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.

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