Functional analysis of MyD88 in astrocytes after spinal cord injury

• Grant number: 23/15455-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2024
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Alexandre Hiroaki Kihara
• Grantee: Isabel Olionis Hirsch
• 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 (SCI) triggers inflammatory response modulated by the action of receptors, including Toll-like receptors (TLRs). After SCI, the accumulation of damaged-associated molecular patterns (DAMPs) activates TLRs throughout MyD88 association with the TLR domain. TLR/MyD88 association leads to NF-ºB translocation to the nucleus, inducing the expression of its target genes. There is evidence that inhibiting the MyD88 pathway may protect cells from inflammation and apoptosis and improve tissue recovery once its signaling is common to most TLRs. Also, the administration of chlorogenic acid reduces inflammation and improves locomotion because of the decrease in MyD88 levels. Previous work by our research group using MyD88 KO animals has shown behavioral improvement in locomotion tests and less glial scar formation. Therefore, this study aims to evaluate the importance of MyD88 in astrocytes after SCI. For that, we will investigate the locomotor consequences in a Cre-flox animal model in which we will be able to selectively knock out MyD88 in astrocytes. With this, we will be able to disclose the role of MyD88 in neuroinflammation, providing new therapeutic strategies for SCI.