Effects of NMDA receptor inhibition on Ouabain-triggered neurogenesis

• Grant number: 24/14502-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2024
• End date: September 30, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Cristoforo Scavone
• Grantee: Mayara Stancey de Haro
• 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

Abstract

As already demonstrated, Ouabaina is a cardiotonic glycoside extracted from plants of the genus Strophantus, and also a mammalian hormone produced in the adrenal cortex and hypothalamus. OAU binds to the Na¿/K¿ membrane protein ATPase, which plays a vital role in cell integrity, given its role in maintaining osmotic balance and its role in cell homeostasis. As a receptor, Na/K-ATPase modulates the growth, migration, and survival of cells in the presence of the glycoside. Glutamate is an amino acid that acts as a neurotransmitter of the CNS and is essential in neurogenesis, and in mature neurons in the formation of memories, from the interaction with the N-Methyl-D-Aspartate (NMDA) receptor, among others, altering gene expression and synaptic activity. Evidence from the literature points to an interaction between Na, K-ATPAse, and the NMDA receptor to trigger signaling related to synaptic plasticity in mature neurons. In addition, previous work carried out in our group showed that Na,K-ATPase signaling exerts a pro-neurogenesis mechanism.In this sense, the objective of the present project is to analyze whether the action of Ouabain/Na,K-ATPase signaling is dependent on the action of NMDA receptors present in neural precursor cells.