Vagus nerve optogenetic stimulation as a strategy to prevent respiratory impairment observed in the 6-hydoxydopamine model of Parkinson's Disease

• Grant number: 24/06266-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2025
• End date: April 30, 2027
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Thiago dos Santos Moreira
• Grantee: Laís Maria Cardoso Cabral
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The population aging emphasizes the need to study prevalent diseases in the elderly,such as Parkinson's Disease (PD), characterized by the progressive death of dopaminergicneurons in the Substantia Nigra. While movement-related symptoms are the most well-known,respiratory dysfunctions account for the majority of deaths associated with this disease. In thelaboratory, the PD model induced by the toxin 6-hydroxydopamine (6-OHDA) has shown areduction in basal respiratory frequency, associated with the degeneration of the retrotrapezoidnucleus (RTN) and the pre-Botzinger complex (preBotC), crucial areas for neural control ofbreathing. Oxidative stress and neuroinflammation mediated by glial cells have been identifiedas contributors to neurodegeneration in this model, making prevention strategies for theseprocesses relevant.It is known that stimulation of the motor and sensory portions of the vagus nerve cansuppress inflammation and serve as an alternative to conventional pharmacological strategies.The project aims to evaluate how this stimulation can suppress neuroinflammation andrespiratory and neuronal changes in an animal model of PD. Vglut-cre Ai32 or Chat-cre Ai32animals will be submitted to bilateral injection of 6-OHDA into the striatum to create themodel, and after 5 days, optogenetic stimulation of the vagus nerve will be performed.Intercostal muscle electrical activity will be recorded after 5 days to obtain respiratoryparameters, and finally, immunohistochemical analysis of the brains will be conducted forneuronal quantification and evaluation of microglia and astrocytes. TNF-± level will bemeasured by ELISA assay in plasma and spleen.The optogenetic strategy is interesting due to its localized action, minimizing sideeffects. In humans, transcutaneous stimulation of the auricular portion of this nerve is possible,providing a less invasive method. Therefore, the project is relevant to research as it allows theexecution of translational science that can benefit patients with PD.