The role of GSK3b in respiratory nuclei in Parkinson's Disease.

• Grant number: 23/09695-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2024
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Bárbara Falquetto
• Grantee: Estela Correia Leandro dos Santos
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Parkinson's disease (PD) is a degenerative disease characterized by the loss of dopaminergic neurons in the Substantia Nigra (SN). Its motor symptoms are widely known as bradykinesia and dyskinesia, but it also has non-classic motor symptoms such as respiratory dysfunction. In rats injected with 6-OHDA in the striatum, a drug that enables the development of a mimetic model of idiopathic PD, there is a loss of neurons in respiratory nuclei such as rotral ventral respiratory group (rVRG) and pre-Bötzinger (preBötC) and significant loss of chemosensitive neurons of the retrotrapezoid nucleus (RTN) in mice. Studies show that oxidative stress is a major mechanism that explains the decrease in number of these neurons. The presence of reactive oxygen species (ROS) leads to activation of central nervous system (CNS) immune cells, such as microglia and astrocytes that respond by releasing pro-inflammatory agents that are often toxic to neuron. Evaluating the signaling pathways of the inflammatory response shows the presence of GSK3², the glycogen synthase kinase 3² that, when inhibited, can protect dopaminergic neurons from harmful agents of neuroinflammation, and thus may also protect the respiratory nuclei from PD degeneration. In this study we will analyze the efects of PD on GSK3-² Tyr216 signaling pathway in respiratory nuclei using Western Blot technique.