Analysis of respiratory activity and respiratory bulbar nuclei in the MitoPark mouse model of Parkinson's Disease

• Grant number: 23/05415-6
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2023
• End date: August 31, 2027
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Ana Carolina Takakura Moreira
• Grantee: Yasmin Cestari Aquino
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Parkinson's disease (PD) is a neurodegenerative disease characterized by a reduction in the number of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Patients with PD present classic motor symptoms, exemplified by tremors and postural instability, and non-classical symptoms such as sleep disturbances and respiratory deficit, which are very little investigated. Recent studies from our laboratory have shown that there was a decrease in respiratory rate and baseline minute ventilation, in addition to the degeneration of respiratory nuclei located in the ventral portion of the medulla in experimental models of PD induced by bilateral injection of 6-hydroxydopamine in the striatum. Currently, more recent genetic model of PD, MitoPark, has been widely used to study the development of non-classical symptoms, since it presents a slower progression of the pathology, similar to that of humans. However, it has not yet been investigated whether the MitoPark model develops respiratory deficits.Thus, the aim of this project is to assess whether the genetic model of PD MitoPark presents central respiratory deficits throughout its development. For this, full body plethysmography will be performed in 20-week-old MitoPark mice and control animals for the analysis of respiratory parameters, and, immediately after, the animals will be euthanized and perfused and will have their brains removed for subsequent immunohistochemical treatments in order to verify the neurons involved in the control of respiratory activity. (AU)