The lncRNA‐AK046375 Upregulates Metallothionein‐2 by Sequestering miR‐491‐5p to Relieve the Brain Oxidative Stress Burden after Traumatic Brain Injury
Wei Tang, Wei-Na Chai, Donglin Du, Yongzhi Xia, Yifan Wu, Li Jiang, Chongjie Cheng, Zongduo Guo, Xiaochuan Sun, Zhijian Huang, Jianjun Zhong
Abstract
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 in vitro and in vivo . 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.