The role of EZH2 on glial transcriptional response and motricity recovery after spinal cord injury

• Grant number: 19/18921-1
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Effective date (Start): February 06, 2020
• Effective date (End): March 20, 2020
• Field of knowledge: Biological Sciences - Genetics
• Principal Investigator: Alexandre Hiroaki Kihara
• Grantee: Felipe Fernandes Correia
• Supervisor: Perrin Florence Evelyne
• Host Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Research place: Mécanismes Moléculaires dans les Démences Neurodégénératives (MMDN), France
• Associated to the scholarship: 18/06316-3 - Functional consequences of EZH2 epigenetical regulation on neurodegeneration and locomotor recovery after spinal cord compression, BP.MS

Abstract

Spinal cord injury (SCI) is a traumatic neurologic disorder that induces the disruption of neuronal communication between the central nervous system (CNS) and the rest of the body. After the primary injury, often caused by mechanical trauma, the condition aggravates due to secondary damages including local tissue inflammation. Nowadays, it is already known that epigenetic-related processes contribute to the spread of CNS damage. Epigenetic is generally related to alterations in the chromatin structure, which are capable to change the availability of genetic information without altering the DNA sequence. Epigenetic mechanisms have been described as a consequence of histone modifications through addition of methyl and acetyl groups. Within this context, global methylation and specially the methylation on lysine 27 of histone 3 produced by enhancer of zeste homolog 2 (EZH2) was related to modulation of inflammatory response in CNS. However, the role of EZH2 on glial cell response after neuronal injury is not well described. The aim of this project is to describe the participation of EZH2 activity on glial cell transcriptional changes and potential motor function recovery through its pharmacological inhibition using GSK343. With the aim of translation to clinics, EZH2 inhibition will be done one hour after SCI, locomotor recovery of the mice will be done with a combination of CatWalkTM and open field analyzes and finally cell specific transcriptomic analysis of microglia will be compared between treated and untreated animals by Fluorescence-activated cell sorting (FACS) and RNA-sequencing. Our project will contribute to describe the specific functions of EZH2 in the glial cell phenotypic changes and open the way to the development of therapeutic strategies aimed to treat SCI. (AU)