Evaluation of the impact of EZH2-related epigenetic changes on polarization and proliferation of spinal cord microglia in vitro

• Grant number: 19/24406-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): June 01, 2020
• Effective date (End): December 31, 2020
• Field of knowledge: Biological Sciences - Genetics
• Principal Investigator: Alexandre Hiroaki Kihara
• Grantee: Bianca Caroline Bobotis
• Host Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Spinal cord injury is a disorder of the central nervous system of crucial medical importance since it has a high prevalence worldwide due to the difficulty of medical treatments and regeneration of neuronal cells. Still, the occurrence of neuronal lesions lead to the release of several factors triggering an inflammatory response. Microglia cells are resident macrophages in neuronal parenchyma heading a phagocytic and inflammatory action when activated by changes in temperature or cell stress. When activated, those microglias can be polarized in M1 or M2 phenotype. The M1 phenotype is responsible for the proinflammatory response, being able to initiate reactions to promote tissue degradation and cell death. The M2 phenotype, on the other hand, provides an anti-inflammatory and regenerative response. Changes in epigenetic mechanisms may lead to some modifications in the establishment of one of these two phenotypes. The histone methylation is the main mechanism that can induce microglia polarization, where the Enhancer of zeste homolog 2 (EZH2), a protein belonging to the Polycomb group, is responsible for initiating transcriptional repression processes after lysine 27 methylation in histone H3, thereby decreasing tissue regeneration. Therefore, the objective of this project is to analyze the pharmacological blockade of EZH2 in HSP (Heat Shock Proteins) activated microglia pure cultures for analysis of their proliferation, polarization and viability.