Banca de DEFESA: CAYO ANTÔNIO SOARES DE ALMEIDA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : CAYO ANTÔNIO SOARES DE ALMEIDA
DATE: 24/05/2024
TIME: 14:00
LOCAL: Sala 209 do Bloco Zeta do Campus São Bernardo do Campo da Universidade Federal do ABC
TITLE:

NOX2 regulates epileptogenesis in temporal lobe epilepsy

PAGES: 92
BIG AREA: Ciências Biológicas
AREA: Fisiologia
SUBÁREA: Fisiologia de Órgãos e Sistemas
SPECIALTY: Neurofisiologia
SUMMARY:

Temporal Lobe Epilepsy (TLE) is often associated with oxidative stress and neuroinflammation. Both processes accompany the changes observed in epileptogenesis and ultimately involve distinct classes of cells, including astrocytes, microglia, and specific neural subtypes. For this reason, molecules associated with oxidative stress and neuroinflammation have been proposed as potential targets for therapeutic strategies. Therefore, the main objective of this study was to evaluate the contribution of the NOX2 enzymatic complex, the main generator of reactive oxygen species (ROS) in the brain, in epileptic seizures induced by pentylenetetrazole (PTZ), in status epilepticus (SE), and in the early stages of epileptogenesis in the KA-induced TLE model, a glutamatergic receptor agonist. In this study, male mice of the C57BL/6J (Wild Type) and gp91phox- (NOX2 Knockout) strains from the animal facility of the Federal University of ABC (CEUA-UFABC: 7873070722) were used. To assess the behavioral progression of seizures, the Racine scale was utilized. Additionally, glial modulation was analyzed through immunofluorescence after the induction of acute seizures. To evaluate alterations during SE and in the latent period, measurements of protein and lipid oxidation were used to infer ROS levels. Western blot assays were performed to assess levels of inflammatory proteins. A multiplex assay based on magnetic beads was employed to determine the immunological modulation from the levels of pro and anti-inflammatory cytokines 2h and 96h after the onset of KA-induced SE in C57BL/6J and gp91phox- mice. Immunofluorescence analysis was conducted in the hippocampus 2h and 96h after the onset of KA-induced SE. Hippocampal neurodegeneration was assessed by the fluoro-jade C assay. Electrophysiological recordings were conducted to analyze epileptiform activity based on the electrocorticographic signature. Primary hippocampal cell cultures were performed to assess cell viability and glial cell modulation after exposure to KA. The results demonstrated that gp91phox- mice are more resistant to acute seizures induced by PTZ; glial cell expression is regulated, as well as their morphology 24h after the induction of an acute epileptic seizure. The SE and epileptogenesis model induced by KA proved to be efficient for studying the influence of NOX2 in the early stages of TLE. Furthermore, neuroinflammatory factors were regulated differently in C57BL/6J and gp91phox- mice, depending on the progression of the disease; moreover, lower cell degeneration was observed in gp91phox- mice and electrophysiological differences between the mouse strains studied. From these findings, it is observed that neuroinflammation plays a crucial role in the onset and development of TLE; furthermore, the disease progression appears to be co-dependent on ROS. By neutralizing the functional aspect of NOX2, improvements were observed in the intensity of acute epileptic seizures, rates of release of neuroinflammatory factors, electrophysiological and glial cell modulation, and ultimately in neurodegeneration. In conclusion, this study may provide new insights into cellular and molecular targets in the treatment of patients refractory to available medication.

COMMITTEE MEMBERS:
Presidente - Interno ao Programa - 1676367 - ALEXANDRE HIROAKI KIHARA
Membro Titular - Examinador(a) Externo ao Programa - 1762353 - MARIA CAMILA ALMEIDA
Membro Titular - Examinador(a) Externo à Instituição - LUIZ ROBERTO GIORGETTI DE BRITTO
Membro Titular - Examinador(a) Externo à Instituição - ROBERTO DE PASQUALE
Membro Titular - Examinador(a) Externo à Instituição - FERNANDO DA SILVA BORGES
Membro Suplente - Examinador(a) Interno ao Programa - 1887027 - FERNANDO AUGUSTO DE OLIVEIRA RIBEIRO
Membro Suplente - Examinador(a) Interno ao Programa - 1994696 - SILVIA HONDA TAKADA
Membro Suplente - Examinador(a) Interno ao Programa - 1872537 - MARCELA BERMUDEZ ECHEVERRY
Membro Suplente - Examinador(a) Externo à Instituição - JULIANE MIDORI IKEBARA
Membro Suplente - Examinador(a) Externo à Instituição - GUILHERME SHIGUETO VILAR HIGA - USP