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Int J Mol Sci ; 21(7)2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32244461

RESUMO

Traumatic brain injury (TBI) dysregulates microRNAs, which are the master regulators of gene expression. Here we investigated the changes in a brain-enriched miR-124-3p, which is known to associate with major post-injury pathologies, such as neuroinflammation. RT-qPCR of the rat tissue sampled at 7 d and 3 months in the perilesional cortex adjacent to the necrotic lesion core (aPeCx) revealed downregulation of miR-124-3p at 7 d (fold-change (FC) 0.13, p < 0.05 compared with control) and 3 months (FC 0.40, p < 0.05) post-TBI. In situ hybridization confirmed the downregulation of miR-124-3p at 7 d and 3 months post-TBI in the aPeCx (both p < 0.01). RT-qPCR confirmed the upregulation of the miR-124-3p target Stat3 in the aPeCx at 7 d post-TBI (7-fold, p < 0.05). mRNA-Seq revealed 312 downregulated and 311 upregulated miR-124 targets (p < 0.05). To investigate whether experimental findings translated to humans, we performed in situ hybridization of miR-124-3p in temporal lobe autopsy samples of TBI patients. Our data revealed downregulation of miR-124-3p in individual neurons of cortical layer III. These findings indicate a persistent downregulation of miR-124-3p in the perilesional cortex that might contribute to post-injury neurodegeneration and inflammation.


Assuntos
Lesões Encefálicas Traumáticas/genética , Lesões Encefálicas Traumáticas/metabolismo , Encéfalo/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Biomarcadores , Lesões Encefálicas Traumáticas/patologia , Córtex Cerebelar , Biologia Computacional , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Transcriptoma , Regulação para Cima
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