Search for miRNAs from extracellular vesicles relevant to epileptogenesis and polygenic risk score of patients who suffered traumatic brain injury

• Grant number: 23/04184-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date until: May 01, 2023
• End date until: January 31, 2026
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Síntia Iole Nogueira Belangero
• Grantee: Beatriz Enguidanos Villena Rueda
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 18/24561-5 - Epileptogenesis, biomarkers and post-traumatic epilepsy, AP.TEM

Abstract

Traumatic brain injury (TBI) is highly frequent in Brazil, with more than 150,000 cases per year, and is a major risk factor for the development of post-traumatic epilepsy (PTE). However, the treatment of TBI-derived PTE is still ineffective. Therefore, it is necessary to investigate new approaches, such as the use of biperiden, an anticholinergic drug. MicroRNAs (miRNAs) from extracellular vesicles (EVs) can help to understand the biological basis of EPT, since they regulate gene expression and can be detected peripherally. EVs are released by various cell types, such as neural cells, and are able to cross the blood-brain barrier. The main objective of this study was to identify patterns of changes in the levels of miRNAs carried by EVs after TBI, which may be related to the development of EPT and/or which are related to the treatment with biperiden. The specific objectives were: a) to find miRNAs associated with PTE, when comparing the group of individuals who developed EPT with those who did not; b) search for miRNAs related to the treatment, when comparing the group of individuals who took placebo with the group who received biperiden; and c) identify the target genes of differentially expressed miRNAs and their biological pathways enriched in epileptogenesis and treatment with biperiden d) calculation of the polygenic risk score for the development of the disease. The collection of study participants is part of a thematic project that included a double-blind and randomized clinical trial. We intend to include 150 individuals who suffered TBI, and the blood collection will be performed 10 days after the trauma and the start of treatment (biperiden or placebo). First, the isolation of EVs from serum will be performed, with a part used for their characterization, according to their size and the presence of membrane proteins. The other part will be used for the extraction of miRNAs followed by the preparation of libraries for the next generation sequencing of the miRNoma (set of miRNAs). DNA will also be extracted from the blood of patients for genotyping. The differential expression analysis of these miRNAs and the calculation of the polygenic risk score will be performed with the aid of bioinformatics tools. Thus, we intend to find miRNAs related to the epileptogenic process after traumatic brain injury and with biperiden, as well as the pathways they regulate; in addition, we expected to calculate the polygenic risk score for the disease. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VILLENA-RUEDA, BEATRIZ ENGUIDANOS; KAJITANI, GUSTAVO SATORU; OTA, VANESSA KIYOMI; HONORATO-MAUER, JESSICA; SANTORO, MARCOS LEITE; BUGIGA, AMANDA VICTORIA GOMES; ROSA, JOICE SANTOS; ASPRINO, PAULA FONTES; MENEGHETTI, PAULA; TORRECILHAS, ANA CLAUDIA; et al. miR-9-5p is Downregulated in Serum Extracellular Vesicles of Patients Treated with Biperiden After Traumatic Brain Injury. Molecular Neurobiology, v. 61, n. 11, p. 13-pg., 2024-04-26. (23/04184-0, 22/14055-0, 18/24561-5, 21/14564-0)