Microglial phenotypes and Parkinson's Disease

• Grant number: 15/03791-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2015
• End date: March 31, 2019
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Luiz Roberto Giorgetti de Britto
• Grantee: Carolina Parga Martins Pereira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 17/09909-2 - Effects of microglial depletion and repopulation in neuronal loss induced by 6-OHDA, a Parkinson's disease model, BE.EP.DR

Abstract

The accelerated populational aging has as a result the increased incidence of diseases associated with aging, as well as the costs of medical treatments. Parkinson's disease (PD) is considered the second most common neurodegenerative disease in elderly people and is characterized by the presence of motor difficulties due to loss of dopaminergic neurons in the striatum. The loss of dopaminergic neurons is a consequence of neuronal degeneration in substancia nigra pars compacta. A major neurotoxins used for PD study in animal models is the 6-hydroxydopamine (6-OHDA), which has as its neurotoxicity mechanism the formation of reactive oxygen species (ROS). The release of ROS by NADPH oxidase (Nox) and microglial activation are early events of neurodegeneration induced by 6-OHDA. The Nox is overactivated in PD, which causes a redox imbalance and cell damage. The microglial cells are the main component of immune defense in the central nervous system and is derived from monocyte lineage cells. Thus, they are similar to the macrophages in both phenotypic and functional characteristics. Studies show that microglia has two types of phenotypes: M1 or classical activation (pro-inflammatory) and M2 or alternative activation (anti-inflammatory). Results from the literature show that the absence of gp91phox subunit of Nox2 in mice increases the amount of microglial cells, which makes the animals protected against dopaminergic neurodegeneration. Based on these results, this study intends to identify the microgial types present in both control mice and in knockout for gp91phox subunit in order to understand the microglial functions in neurodegeneration and neuroprotection processes. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

PEREIRA, Carolina Parga Martins. Microglial role in a model of Parkinsons disease induced by 6-hydroxydopamine.. 2019. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.