OUABAIN EFFECTS ON CHANGES IN MITOCHONDRIAL FUNCTION AND THE NEUROGENESIS PROCESS IN CORTICAL NEURONAL CELLS EXPOSED TO ROTENONE

• Grant number: 23/01789-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2023
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Cristoforo Scavone
• Grantee: Vitória Cristina Araujo
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/06009-6 - Neuroplasticity -induced by challenge Na, K-ATPase, Klotho, glutamate, and neuroinflammation signaling cascades to reveal new therapeutic targets for aging and neurodegenerative diseases, AP.TEM
• Associated scholarship(s): 24/10559-0 - Bipolar disorder models: Oxidative stress response in neuronal cortical primary culture from Poly (I:C) treated with Ouabain, BE.EP.IC

Abstract

The development of the central nervous system is a phase that ranges from the emergence of neuronal cells and their interactions with each other, to synaptic pruning, in which certain connections are extinguished. This entire process is highly dependent on ATP molecules, on managing the formation of reactive oxygen species, and also on controlling Ca2+ ion levels, and is therefore directly linked to mitochondrial activity. In this sense, it is known that rotenone, an inhibitor of mitochondrial complex 1, is able to reduce the amount and size of neuronal extensions, proving to be harmful to neurodevelopment. In contrast, ouabain, a Na+/K+ ATPase inhibitor compound, was associated with the activation of several signaling pathways linked to neuroprotection against inflammatory conditions. Furthermore, it is known that ouabain has interaction sites located in the mitochondria, although the exact nature of this interaction is not known. Taking into account the importance of mitochondrial function for the successful development of the CNS, and that failures in such development are associated with several neuropsychiatric disorders, such as Schizophrenia, Alzheimer's and Parkinson's Disease, the project aims to evaluate the potential of ouabain in protecting or reversing cellular damage caused by Rotenone administration. For this, tests will be carried out to evaluate the neuronal structure, as well as the mitochondrial activity in primary cortical cultures treated with both substances.