Investigating the role of microglial activity in respiratory impairments and neurodegeneration in Parkinson's Disease: the impact of estrogen deficiency

• Grant number: 24/16971-0
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: March 01, 2025
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Ana Carolina Takakura Moreira
• Grantee: Giovanna Matos Rodrigues
• Supervisor: Anna Victoria Rotberg Molofsky
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of California, San Francisco (UCSF), United States
• Associated to the scholarship: 22/12788-0 - Role of female sex hormones on respiratory parameters during the development of Parkinson's Disease in the 6-OHDA model in female mice, BP.IC

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by classic motor symptoms, such as tremors and postural instability. In addition, PD can present with non-classical symptoms, which may include respiratory deficits, one of the leading causes of death in affected individuals. Previous studies have shown that the respiratory deficits observed in PD may be linked to damage in neural areas involved in respiratory control. Neuroinflammation has been suggested as a key factor in the pathology of PD. This immune response involves interactions among several cell types, especially microglia, immune cells that constitute 10% of brain cells, and can enter a "reactive state" producing pro-inflammatory factors that ultimately lead to progressive neuronal damage.PD is the second most common neurodegenerative disease globally, and although it affects both sexes, the incidence of the disease is typically twice as high in men compared to women in most populations, and the onset of symptoms tends to occur at an earlier age. Epidemiological and clinical evidence suggests that female sex hormones may influence the development and progression of PD. Our previous work has demonstrated that ovariectomy in female mice exacerbates neuroanatomical and respiratory functional changes in the 6-hidroxidopamine-induced PD model, suggesting that ovarian hormones may play a crucial role in protecting against neuroinflammation associated with PD. These results emphasize the need for further investigation into the hormonal interactions in neurodegenerative diseases, which could lead to novel therapeutic approaches. Thus, the aim of the present project is to investigate the role of microglial cell activity in the neurodegenerative processes affecting the respiratory control nuclei, with a specific focus on the impact of reduced estrogen levels.