The role of MyD88 signaling pathway in vivo and in vitro epilepsy induced by kainic acid.

• Grant number: 21/13980-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2022
• End date: October 31, 2024
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Alexandre Hiroaki Kihara
• Grantee: Renan Paschoalino Pongilio
• Host Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Santo André , SP, Brazil

Abstract

Temporal lobe epilepsy (ELT) is a neuronal disorder characterized by recurrent and spontaneous seizures that originate from the temporal lobe. The seizures are caused by the heightened neuronal excitability and synchronicity. To understand the phisiophatology of ELT, animal models are indispensable tools. Between them, we can cite the model based on intrahipocampal kainic acid (KA) administration. It is known that glial cells are responsible for diverse functions in epileptogenesis, especially in the coordination of the inflamatory response, involving toll-like receptors (TLR). Inside the sinalization pathways of TLRs, the protein myeloid differentiation primary response (MyD88) plays an important role. Beyond participating in TLR sinalization, it is also necessary for interleucin-1 receptor (IL1R) sinalization. In this work, we pretend to investigate the role of MyD88 in the establishment of epilepsy. For this, we will use purified cellular cultures from specific cell types from hipocampal tissue and identify in them MyD88. Doing this, we pretend to understand the expression of MyD88 in neurons, astrocytes, and microglia, in which MyD88 modules distinct events. It will also be employed C57/BL6 mice, wild type and knockout (MyD88), for subsequent electrophysiological and immunological analysis to understand the contribution of MyD88 in ELT. With this work, we intend to clarify the mechanism by which MyD88 impacts on the epilepsy establishment, opening new possibilities for therapeutic strategy. (AU)