Mitochondrial Dysfunction and Changes in High-Energy Compounds in Different Cellular Models Associated to Hypoxia: Implication to Schizophrenia

Autor(es)

Souza e Silva, Luiz Felipe ^[1] ; Brito, Mariana Dutra ^[1] ; Camargo Yuzawa, Jessica Mayumi ^[1] ; Rosenstock, Tatiana Rosado ^[1]

Afiliação do(s) autor(es)

^[1] Santa Casa de Sao Paulo Sch Med Sci, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 9, DEC 2 2019.
• Citações Web of Science: 0

Resumo

Schizophrenia (SZ) is a multifactorial mental disorder, which has been associated with a number of environmental factors, such as hypoxia. Considering that numerous neural mechanisms depends on energetic supply (ATP synthesis), the maintenance of mitochondrial metabolism is essential to keep cellular balance and survival. Therefore, in the present work, we evaluated functional parameters related to mitochondrial function, namely calcium levels, mitochondrial membrane potential, redox homeostasis, high-energy compounds levels and oxygen consumption, in astrocytes from control (Wistar) and Spontaneously Hypertensive Rats (SHR) animals exposed both to chemical and gaseous hypoxia. We show that astrocytes after hypoxia presented depolarized mitochondria, disturbances in Ca2+ handling, destabilization in redox system and alterations in ATP, ADP, Pyruvate and Lactate levels, in addition to modification in NAD(+)/NADH ratio, and Nfe2l2 and Nrf1 expression. Interestingly, intrauterine hypoxia also induced augmentation in mitochondrial biogenesis and content. Altogether, our data suggest that hypoxia can induce mitochondrial deregulation and a decrease in energy metabolism in the most prevalent cell type in the brain, astrocytes. Since SHR are also considered an animal model of SZ, our results can likewise be related to their phenotypic alterations and, therefore, our work also allow an increase in the knowledge of this burdensome disorder. (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
• Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
• Processo FAPESP: 16/12039-7 - A modulação de lisinas(K)-deacetilases e o seu papel no metabolismo, dinâmica e degradação mitocondrial: possível neuroproteção para a Esclerose Lateral Amiotrófica
• Beneficiário: Mariana Dutra Brito
• Linha de fomento: Bolsas no Brasil - Mestrado
• Processo FAPESP: 15/25595-2 - Sirtuínas na neuropatologia da esquizofrenia: implicação contra a disfunção mitocondrial na hipóxia
• Beneficiário: Luiz Felipe Souza e Silva
• Linha de fomento: Bolsas no Brasil - Mestrado