Banca de DEFESA: DELMA HOLANDA DE ALMEIDA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : DELMA HOLANDA DE ALMEIDA
DATE: 02/03/2023
TIME: 09:00
LOCAL: ICBS
TITLE:

DIFFERENTIAL GENE EXPRESSION IN PATIENTS WITH TEMPORAL LOBE EPILEPSY: SYSTEMATIC REVIEW COUPLED TO BIOINFORMATICS ANALYSIS

KEY WORDS:

epileptogenesis, hippocampal sclerosis, gene expression,
pharmacoresistance.

PAGES: 50
BIG AREA: Ciências Biológicas
AREA: Genética
SUBÁREA: Genética Humana e Médica
SUMMARY:

Temporal Lobe Epilepsy associated with Hippocampal Sclerosis I (TLE-
EH) is the most common type of partial epilepsy in adults. Characterized by a complex
pathological process, which involves neuronal losses, reorganization of synapses,
inflammation and molecularly by the global reorganization of gene expression, in
addition to a refractoriness of (30-40%) of patients to existing antiepileptic drugs
(AEDs). Many gene expression studies, both in animal models and in humans, seek to
investigate the molecular alterations underlying the epileptogenic process, but due to the
heterogeneity of the studies, it was necessary to carry out a careful systematic review
with the objective of identifying the consistent genes that participate of the
epileptogenic process in humans with ELT-EH. Methodology: This is a systematic
review registered in PROSPERO under the ID number: CRD42020180745, according to
the protocol described by prism 2020. We carried out the search on January 30, 2021,
using the PubMed and LILACS databases. , EMBASE and SIGLE, open gray, with the
keywords: “Gene Expression” AND “Epilepsy”; “Gene Expression” AND “Seizure”;
“Protein Expression” AND “Seizure” AND “Human”; “Protein Expression” AND
“Epilepsy” AND “Human”. The results extracted and analyzed had a focus on gene
expression data, as well as tissue, molecules, and techniques evaluated. In addition, for
genes that are differentially expressed and consistent in more than one study, we
proceed with bioinformatics analyses, such asassessingg the functional categories of the
Gene Ontology (GO) and searching for regulators of gene expression, such as validated
microRNAs (miRs) experimentally and analysis of transcriptional factors. To reduce
biases, three researchers independently performed all steps and inclusion and exclusion
criteria were applied for study eligibility. Results: 202 studies met the eligibility
criteria, with 448 genes studied in ELT-EH. 95 genes at least twice, of which 47 showed
consistent data. Thirty-four genes were up- regulated in the brain, seven down regulated
and six genes showed no statistically significant difference. The 41 genes were
submitted to functional analysis in GO to obtain pathways in molecular function,
cellular component,s and biological processes. To analyzes activating ways; we got
seven genes with the potential for transcriptional regulation. As for the analysis of
miRs, for the 34 genes up-regulated in epileptic tissue, we found 105 validated miRs in
total for the seven genes with reduced expression. Furthermore, we found more than

three validated miRs from the overexpressed genes: BCL2, DNMT1, TLR4, BDNF,
NFKB1, VEGFA, CASP3, TNF, COX2 and from the negatively regulated genes
GSK3B AND HCN2. Conclusion: In this sense, our work provides a compilation of
vital information on gene expression associated with drug-resistant ELT and its
regulators. In addition, it subsidizes precious data for future studies of discovering and
validating new therapeutic targets based on manipulating gene expression in mTLE.

BANKING MEMBERS:
Presidente - 2579081 - DANIEL LEITE GOES GITAI
Interno(a) - 1878467 - GUSTAVO GOMES DE ARAUJO
Interno(a) - 2033893 - MARCELO DUZZIONI
Externo(a) ao Programa - 1306075 - RENATO SANTOS RODARTE
Externo(a) à Instituição - AXEL HELMUT RULF COFRE - CESMAC