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Glutamate and Epilepsy: The Effect of Artificial and Biological Astrocytes in a Experimental Model Induced by Pilocarpine

Grant number: 23/07571-5
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): February 01, 2024
Status:Discontinued
Field of knowledge:Humanities - Psychology - Physiological Psychology
Principal Investigator:Milena de Barros Viana
Grantee:Jéssica Alves Lemes
Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil

Abstract

Epilepsy is a chronic neurologic disease, characterized by recurrent seizures, which are a result of excessive electrical discharges in a group of brain cells. Potential dysregulation in glutamatergic mechanisms has been a longstanding proposed mechanism in epilepsy. Increases in extracellular glutamate can lead to a buildup of glutamate in the synapse and overactivation of the glutamate receptors, resulting in excitotoxicity and ultimately, cell death. The resulting hypothesis is that a reduction in extracellular brain glutamate concentration, and thereby a reduction in glutamate excitotoxicity, can diminish epileptogenesis. Synthetic biology has emerged, during the last years, as a promising field. The focus is on the development of micro and nanostructures, including artificial cells, organelles and enzymes, the so-called micro or nanoreactors. Some of these structures are equipped with glutamate dehydrogenase and glutathione reductase, which decrease extracellular glutamate levels producing reduced glutathione. The purpose of the present study is to investigate the in vivo behavioral and neurobiological effects of these microreactors in a chronic model of epilepsy (induced by intra-dorsal hippocampus administration of pilocarpine). The severity of the seizures will be evaluated in an open field according to a modified Racine scale, immediately after pilocarpine administration, and subsequently in different moments after pilocarpine administration: open field (day 20), elevated plus-maze (day 23), splash test (day 26) and object reallocation test (28-30). Thirty minutes after behavioral evaluation, animals will be euthanized and their brains processed for the measurement of neuroinflammation, oxidative stress, neurodegeneration and neurogenesis parameters. This project is a research collaboration between the Federal University of São Paulo and the University of Lisbon.

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