miR-9-5p is Downregulated in Serum Extracellular Vesicles of Patients Treated with Biperiden After Traumatic Brain Injury.

Autor: Villena-Rueda BE; Genetics Division, Department of Morphology and Genetics, Universidade Federal de São Paulo (UNIFESP), Rua Botucatu, 740, Vila Clementino, São Paulo, - 04023900, Brazil.; LiNC - Laboratory of Integrative Neuroscience, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Kajitani GS; Genetics Division, Department of Morphology and Genetics, Universidade Federal de São Paulo (UNIFESP), Rua Botucatu, 740, Vila Clementino, São Paulo, - 04023900, Brazil.; LiNC - Laboratory of Integrative Neuroscience, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Ota VK; Genetics Division, Department of Morphology and Genetics, Universidade Federal de São Paulo (UNIFESP), Rua Botucatu, 740, Vila Clementino, São Paulo, - 04023900, Brazil.; LiNC - Laboratory of Integrative Neuroscience, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Honorato-Mauer J; Genetics Division, Department of Morphology and Genetics, Universidade Federal de São Paulo (UNIFESP), Rua Botucatu, 740, Vila Clementino, São Paulo, - 04023900, Brazil.; LiNC - Laboratory of Integrative Neuroscience, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Santoro ML; LiNC - Laboratory of Integrative Neuroscience, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.; Molecular Biology Division, Department of Biochemistry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Bugiga AVG; Genetics Division, Department of Morphology and Genetics, Universidade Federal de São Paulo (UNIFESP), Rua Botucatu, 740, Vila Clementino, São Paulo, - 04023900, Brazil.; LiNC - Laboratory of Integrative Neuroscience, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Rosa JS; LiNC - Laboratory of Integrative Neuroscience, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.; Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Asprino PF; Molecular Oncology Center, Hospital Sírio-Libanês, São Paulo, Brazil., Meneghetti P; Laboratório de Imunologia Celular E Bioquímica de Fungos E Protozoários, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Department of Pharmaceutical Sciences, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Torrecilhas AC; Laboratório de Imunologia Celular E Bioquímica de Fungos E Protozoários, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Department of Pharmaceutical Sciences, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Intasqui P; Human Reproduction Section, Division of Urology, Department of Surgery, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Bertolla RP; Human Reproduction Section, Division of Urology, Department of Surgery, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Foresti ML; Department of Physiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.; Instituto D'Or de Pesquisa E Ensino (IDOR), São Paulo, Brazil., da Graça Naffah-Mazzacoratti M; Department of Physiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., de Moraes Mello LEA; Department of Physiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.; Instituto D'Or de Pesquisa E Ensino (IDOR), São Paulo, Brazil., Belangero SI; Genetics Division, Department of Morphology and Genetics, Universidade Federal de São Paulo (UNIFESP), Rua Botucatu, 740, Vila Clementino, São Paulo, - 04023900, Brazil. sinbelangero@gmail.com.; LiNC - Laboratory of Integrative Neuroscience, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. sinbelangero@gmail.com.; Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. sinbelangero@gmail.com.
Jazyk: angličtina
Zdroj: Molecular neurobiology [Mol Neurobiol] 2024 Nov; Vol. 61 (11), pp. 9595-9607. Date of Electronic Publication: 2024 Apr 26.
DOI: 10.1007/s12035-024-04194-5
Abstrakt: Traumatic brain injury (TBI) is a prevalent and debilitating condition, which often leads to the development of post-traumatic epilepsy (PTE), a condition that yet lacks preventive strategies. Biperiden, an anticholinergic drug, is a promising candidate that has shown efficacy in murine models of PTE. MicroRNAs (miRNAs), small regulatory RNAs, can help in understanding the biological basis of PTE and act as TBI- and PTE-relevant biomarkers that can be detected peripherally, as they are present in extracellular vesicles (EVs) that cross the blood-brain barrier. This study aimed to investigate miRNAs in serum EVs from patients with TBI, and their association with biperiden treatment and PTE. Blood samples of 37 TBI patients were collected 10 days after trauma and treatment initiation in a double-blind clinical trial. A total of 18 patients received biperiden, with three subjects developing PTE, and 19 received placebo, with two developing PTE. Serum EVs were characterized by size distribution and protein profiling, followed by high-throughput sequencing of the EV miRNome. Differential expression analysis revealed no significant differences in miRNA expression between TBI patients with and without PTE. Interestingly, miR-9-5p displayed decreased expression in biperiden-treated patients compared to the placebo group. This miRNA regulates genes enriched in stress response pathways, including axonogenesis and neuronal death, relevant to both PTE and TBI. These findings indicate that biperiden may alter miR-9-5p expression in serum EVs, which may play a role in TBI resolution.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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