ENTERIC AND CENTRAL NEUROINFLAMATION IN AN ANIMAL MODEL OF PARKINSON'S DISEASE: THE ROLE OF NG2 GLIA CELLS

• Grant number: 23/13357-6
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: December 29, 2023
• End date: February 28, 2024
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Elaine Aparecida Del Bel Belluz Guimarães
• Grantee: Bruna Araujo Milan
• Supervisor: Laura Mascaraque
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Instituto Cajal, Spain
• Associated to the scholarship: 23/01986-9 - Effect of probiotic therapy on enteric and central neuroinflammation in an animal model of Parkinson's disease, BP.IC

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease, and its occurrence and progression have been extensively studied. However, the pathogenesis of PD is still far from fully understood. Neuroinflammation is one of the neurobiological characteristics of PD pathology, with this brain-mediated inflammatory response primarily mediated by the activation of glial cells. Recently, the scientific community has turned its attention to a population of non-neuronal cells known as NG2 cells regarding neuroinflammation in neurodegenerative diseases. The role of NG2-glia cells in neuroinflammatory conditions has been clarified. These cells actively sense their microenvironment by continuously extending filopodia, as demonstrated in previous studies. This capability enables them to monitor and respond to local changes effectively and this population adapt to various pathological conditions such as neurodegenerative disorders, demyelination, and traumatic injuries. When exposed to inflammatory signals, they adopt a reactive phenotype, resulting in a diverse appearance that resembles microglial cells. This activation phenotype involves shortening of the cell cycle, retracting long, multi-branched processes into shorter, thicker ones, and enlarging the cell body. The specific functions of NG2-expressing cells are only beginning to be understood, with limited analysis in the context of conditions like Parkinson's disease and levodopa-induced dyskinesia. The brain-gut axis is a bidirectional communication channel that emerges as a potential diagnostic and therapeutic target for central nervous system diseases, such as Parkinson's disease. The increasing body of evidence pointing to a two-way connection between the gut and the brain indicates that probiotics might offer a potential strategy for enhancing gut microbiota health and stability, potentially delaying or preventing neurodegenerative diseases. In fact, fecal microbiota transplantation, antibiotic therapy and probiotics reverse the composition of intestinal microbiota, and reverse the pathological activation of astrocytes. This is a beneficial therapeutic strategy not only in gastrointestinal diseases but also in brain, even if the underlying mechanism diseases still remains to be explored. Our aim in this project is to assess the influence of probiotic use in an animal model of Parkinson's disease on central NG2 glial cells.