Banca de QUALIFICAÇÃO: CAYO ANTÔNIO SOARES DE ALMEIDA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : CAYO ANTÔNIO SOARES DE ALMEIDA
DATE: 14/04/2023
TIME: 14:00
LOCAL: Sala 210 do Bloco Zeta do Campus de São Bernardo do Campo da Universidade Federal do ABC
TITLE:

NOX2 regulates epileptogenesis in temporal lobe epilepsy

PAGES: 72
BIG AREA: Ciências Biológicas
AREA: Fisiologia
SUBÁREA: Fisiologia de Órgãos e Sistemas
SPECIALTY: Neurofisiologia
SUMMARY:

It is widely established that temporal lobe epilepsy (TLE) is often related to oxidative stress and neuroinflammation. Both processes subserve alterations 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 response and neuroinflammation have been proposed as potential targets for therapeutic strategies. Therefore, the main objective of this study is to evaluate the contribution of the NOX2 enzyme complex in status epilepticus and early stages of epileptogenesis in the TLE model induced by kainic acid and status epilepticus induced by pentylzenotrelone (PTZ). In this study, male mice of the C57BL/6 or Wild Type (WT) strain and male mice of the NOX2 (popular name) or Cybbtm1Din strain from the animals’ facilities of the Federal University of ABC were required (CEUA-UFABC: 7873070722). To determine the levels of reactive oxidative species (ROS) in the two strains, protein and lipid oxidation measurements were used. Hippocampal primary cell cultures of the C57BL/6 and NOX2 mice were performed to evaluate the cell viability after exposing them to kainic acid, an agonist of the kainate receptor. To evaluate behavioral seizure scoring, PTZ was utilized, inducing status epilepticus in C57BL/6 and NOX2 KO mice. To determine the concentration of pro- and anti-inflammatory cytokines 2h and 96h after the onset of SE induced by kainic acid on C57BL/6 and NOX2 KO mice, a multiplex assay was used. By using immunohistochemistry, it was analyzed the effects of NOX2 KO on astrocytes and hippocampus degeneration 2h and 96h after the onset of SE induced by kainic acid. The results demonstrated that NOX2 KO mice are more resistant to status epilepticus induced-PTZ; also it was observed less cell degeneration in NOX2 KO mice. Moreover, the results showed that neuroinflammatory factors are regulated differently in C57BL/6 and NOX2 mice, as demonstrated in the pro- and anti-inflammatory cytokines analyses. This regulation also depends on the disease’s evolution. From these findings, it is observed that neuroinflammation plays a crucial role in the installation and development of TLE; in addition, the mechanism of evolution of this disease is codependent on ROS. By neutralizing the functional aspect of NOX2, one of the main generators of ROS, it is possible to observe an improvement in the release rates of neuroinflammatory factors, in neurodegeneration and the behavior of epileptic seizures. In conclusion, this study may bring new insights into cellular and molecular targets in the treatment of patients refractory to available medication.

COMMITTEE MEMBERS:
Presidente - Interno ao Programa - 1994696 - SILVIA HONDA TAKADA
Membro Titular - Examinador(a) Externo à Instituição - ANGELA CRISTINA DO VALLE - USP
Membro Titular - Examinador(a) Externo à Instituição - RICARDO MARIO ARIDA - UNIFESP
Membro Suplente - Examinador(a) Interno ao Programa - 1887027 - FERNANDO AUGUSTO DE OLIVEIRA RIBEIRO
Membro Suplente - Examinador(a) Externo à Instituição - JULIANE MIDORI IKEBARA