Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China 400016.
Oxid Med Cell Longev. 2022 Feb 16;2022:8188404. doi: 10.1155/2022/8188404. eCollection 2022.
We previously discovered that traumatic brain injury (TBI) induces significant perturbations in long noncoding RNA (lncRNA) levels in the mouse cerebral cortex, and lncRNA-AK046375 is one of the most significantly changed lncRNAs after TBI. lncRNA-AK046375 overexpression and knockdown models were successfully constructed both and . In cultured primary cortical neurons and astrocytes, lncRNA-AK046375 sequestered miR-491-5p, thereby enhancing the expression of metallothionein-2 (MT2), which ameliorated oxidative-induced cell injury. In addition, upregulated lncRNA-AK046375 promoted the recovery of motor, learning, and memory functions after TBI in C57BL/6 mice, and the underlying mechanism may be related to ameliorated apoptosis, inhibited oxidative stress, reduced brain edema, and relieved loss of tight junction proteins at the blood-brain barrier in the mouse brain. Therefore, we conclude that lncRNA-AK046375 enhances MT2 expression by sequestering miR-491-5p, ultimately strengthening antioxidant activity, which ameliorates neurological deficits post-TBI.
我们之前发现，创伤性脑损伤（TBI）会导致小鼠大脑皮层中的长非编码 RNA（lncRNA）水平发生显著变化，lncRNA-AK046375 是 TBI 后变化最显著的 lncRNA 之一。成功构建了 lncRNA-AK046375 的过表达和敲低模型，无论是在体外培养的原代皮质神经元和星形胶质细胞中，还是在体内 C57BL/6 小鼠的 TBI 模型中。lncRNA-AK046375 可以与 miR-491-5p 结合，从而增强金属硫蛋白 2（MT2）的表达，减轻氧化应激诱导的细胞损伤。此外，上调的 lncRNA-AK046375 可促进 C57BL/6 小鼠 TBI 后运动、学习和记忆功能的恢复，其潜在机制可能与减轻细胞凋亡、抑制氧化应激、减少脑水肿以及缓解血脑屏障紧密连接蛋白丢失有关。因此，我们得出结论，lncRNA-AK046375 通过与 miR-491-5p 结合来增强 MT2 的表达，最终增强抗氧化活性，从而改善 TBI 后的神经功能缺损。
