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

Author(s)

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

Affiliation

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

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 9, DEC 2 2019.
• Web of Science Citations: 0

Abstract

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)

• 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: 16/12039-7 - Lysine(K)-deacetylases modulation and its role in mitochondrial metabolism, dynamics and degradation: possible neuroprotection for amyotrophic lateral sclerosis
• Grantee: Mariana Dutra Brito
• Support Opportunities: Scholarships in Brazil - Master
• 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