Sun Liqian, Liu Aihua, Zhang Jingbo, Ji Wenjun, Li Youxiang, Yang Xinjian, Wu Zhongxue, Guo Jian
Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
Department of Neurosurgery, Shandong province Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong, China.
Behav Brain Res. 2018 Mar 15;340:126-136. doi: 10.1016/j.bbr.2016.09.020. Epub 2016 Sep 11.
Dysregulated microRNAs (miRNAs) have been reported to involve in the pathophysiological process of traumatic brain injury (TBI), and modulate autophagy-related genes (ATGs) expression. Our previous studies showed that neuronal autophagy was activated in the injury hippocampus post- TBI and associated with neurological and cognitive impairments. The present study was designed to investigate the possible role of miR-23b in TBI-induced cognitive impairments. We found the overexpression of miR-23b conferred a better neuronprotective effects after TBI by decreasing lesion volume, alleviating brain edema, inhibiting neuron apoptosis and attenuating long-term neurological deficits, and most interestingly, improving cognitive impairments. To further explore the molecular underlying this neuronprotection, we evaluated autophagic activity and ATG12 expression in the injury hippocampus CA1 region. The results identified that miR-23b directly targeted to the 3'UTR region of ATG12 mRNA to suppress the activation of neuronal autophagy by a dual-luciferase reporter system. Notably, overexpression of ATG12 abrogated the neuronprotective effects of miR-23b on TBI-induced neurological and cognitive impairments. Taken together, these date revealed inhibition of ATG12-mediated autophagic activity by miR-23b overexpression might be involve in cognitive improvement after TBI, indicating that miR-23b might be a potential therapeutic target for TBI.
据报道，失调的微小RNA（miRNA）参与创伤性脑损伤（TBI）的病理生理过程，并调节自噬相关基因（ATG）的表达。我们之前的研究表明，TBI后损伤的海马体中神经元自噬被激活，并与神经和认知障碍有关。本研究旨在探讨miR-23b在TBI诱导的认知障碍中的可能作用。我们发现，miR-23b的过表达通过减小损伤体积、减轻脑水肿、抑制神经元凋亡和减轻长期神经功能缺损，在TBI后具有更好的神经保护作用，最有趣的是，还能改善认知障碍。为了进一步探索这种神经保护作用的分子机制，我们评估了损伤海马体CA1区的自噬活性和ATG12的表达。结果表明，miR-23b通过双荧光素酶报告系统直接靶向ATG12 mRNA的3'UTR区域，抑制神经元自噬的激活。值得注意的是，ATG12的过表达消除了miR-23b对TBI诱导的神经和认知障碍的神经保护作用。综上所述，这些数据表明，miR-23b过表达抑制ATG12介导的自噬活性可能参与了TBI后的认知改善，表明miR-23b可能是TBI的一个潜在治疗靶点。
