Chronic Regulation of miR-124-3p in the Perilesional Cortex after Experimental and Human TBI
| Autor: | Vuokila, Niina, Aronica, Eleonora, Korotkov, Anatoly, van Vliet, Erwin Alexander, Nuzhat, Salma, Puhakka, Noora, Pitkänen, Asla |
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| Přispěvatelé: | Cellular and Computational Neuroscience (SILS, FNWI), Pathology, ANS - Cellular & Molecular Mechanisms, APH - Aging & Later Life, APH - Mental Health, Graduate School |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Down-Regulation Real-Time Polymerase Chain Reaction Article Rats Sprague-Dawley lcsh:Chemistry Cerebellar Cortex Brain Injuries Traumatic miR-124-3p Animals Humans lcsh:QH301-705.5 microRNA Gene Expression Profiling traumatic brain injury Brain Computational Biology bioinformatics Rats Up-Regulation MicroRNAs lcsh:Biology (General) lcsh:QD1-999 biomarker Female epileptogenesis Transcriptome Biomarkers |
| Zdroj: | International Journal of Molecular Sciences, Vol 21, Iss 2418, p 2418 (2020) International Journal of Molecular Sciences International Journal of Molecular Sciences, 21(7):2418. Multidisciplinary Digital Publishing Institute (MDPI) International journal of molecular sciences, 21(7):2418. Multidisciplinary Digital Publishing Institute (MDPI) |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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