A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
Department of (Neuro)pathology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Int J Mol Sci. 2020 Mar 31;21(7):2418. doi: 10.3390/ijms21072418.
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, < 0.05 compared with control) and 3 months (FC 0.40, < 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 < 0.01). RT-qPCR confirmed the upregulation of the miR-124-3p target in the aPeCx at 7 d post-TBI (7-fold, < 0.05). mRNA-Seq revealed 312 downregulated and 311 upregulated miR-124 targets ( < 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.
创伤性脑损伤 (TBI) 会使 microRNAs 失调，而 microRNAs 是基因表达的主要调控因子。在这里，我们研究了一种在大脑中丰富表达的 miR-124-3p 的变化，已知该 microRNA 与主要的损伤后病理学有关，如神经炎症。对坏死病变核心周围皮层（aPeCx）中的大鼠组织进行 RT-qPCR 分析，发现在损伤后 7 天（FC 0.13， < 0.05 与对照组相比）和 3 个月（FC 0.40， < 0.05）时 miR-124-3p 下调。原位杂交证实了 miR-124-3p 在损伤后 7 天和 3 个月在 aPeCx 中的下调（均 < 0.01）。RT-qPCR 证实了 miR-124-3p 靶基因在损伤后 7 天在 aPeCx 中的上调（7 倍， < 0.05）。mRNA-Seq 显示有 312 个下调和 311 个上调的 miR-124 靶基因（ < 0.05）。为了研究实验结果是否转化为人类，我们对 TBI 患者颞叶尸检样本进行了 miR-124-3p 的原位杂交。我们的数据显示 miR-124-3p 在皮质层 III 的单个神经元中下调。这些发现表明，miR-124-3p 在损伤周围皮层中的持续下调可能导致损伤后神经退行性变和炎症。
