Differential expression of microRNAs in the brains of mice subjected to increasing grade of mild traumatic brain injury
Differential expression of microRNAs in the brains of mice subjected to increasing grade of mild traumatic brain injury
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DOI：
10.1080/02699052.2016.1213420
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发表时间：
2017-01-01
期刊：
影响因子：
1.9
通讯作者：
Maheshwari, Radha K.
中科院分区：
文献类型：
--
作者：
Chandran, Raghavendar;Sharma, Anuj;Maheshwari, Radha K.
目的：为了研究mTBI中的异质性对小鼠脑中miRNA表达的影响，并鉴定被调节的miRNA靶向的分子通路。使用TaqMan啮齿动物miRNA阵列评估miRNA表达。生物信息学分析使用DIANA miRPath工具和Influencity Pathway Analysis软件进行。结果：损伤组小鼠脑组织未见明显病理改变，但损伤组小鼠脑组织中的miRNA表达谱发生了显著变化。总体miRNA分析表明，除了最严重等级的mTBI之外，从损伤后24小时至第7天，调节的miRNA的数量有减少的趋势。典型的钙信号通路、突触通路和轴突导向通路是调控miRNAs的主要靶点。网络相关性分析表明调制的miRNA和推定的蛋白质生物标志物TBI.Conclusions之间的相互作用：数据表明，不同强度的mTBI诱导的差异miRNA表达谱在脑损伤后。钙和突触信号传导等途径是调节的miRNA的主要靶点，并可能在mTBI的病理生理学中发挥作用。
Objective: To investigate the effect of heterogeneity in mTBI on miRNA expression in mouse brain and to identify molecular pathways targeted' by the modulated miRNAs.Methods: A weight drop device was used to induce four, increasing grades of mTBI. MiRNA expression was evaluated using TaqMan rodent miRNA arrays. Bioinformatics analysis was done using the DIANA miRPath tool and Ingenuity Pathway Analysis software. Histology of brain sections was evaluated using H&E staining.Results: No histologic lesions were observed in the brains of injured mice; however, significant modulation in miRNA expression profile was observed. Global miRNA profiling, indicated a trend Of decrease in the number of modulated' miRNAs from 24 hours to day 7 post-injury, except for the most severe grade of mTBI. Canonical pathways like calcium signalling, synaptic pathways and axon guidance pathway were the major targets of the modulated miRNAs. Network correlation analyses indicated an interaction between the modulated miRNAs and putative protein biomarkers of TBI.Conclusions: The data demonstrated that varying intensities of mTBI induced a differential miRNA expression profile in the brain post-injury. Pathways such as calcium and synaptic signalling, were major targets of modulated miRNAs and may play a role in the pathophysiology of mTBI.