Brain Metabolic Changes in Rats following Acoustic Trauma.
Brain Metabolic Changes in Rats following Acoustic Trauma.
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DOI：
10.3389/fnins.2017.00148
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发表时间：
2017
影响因子：
4.3
通讯作者：
Zheng Y
中科院分区：
文献类型：
--
作者：
He J;Zhu Y;Aa J;Smith PF;De Ridder D;Wang G;Zheng Y
听力损失和耳鸣的主要原因是什么？然而，声损伤对系统生物学的影响尚未完全了解。人们越来越认识到，由声损伤引起的耳鸣不太可能由单一的病理来源产生，而是一个复杂的变化网络，不仅涉及听觉系统，还涉及与记忆，情绪和压力有关的系统。耳鸣研究中的一个明显而重大的差距是缺乏反映这种互动的“耳鸣引起”网络后果的生物标志物。在这项研究中，我们首次尝试使用代谢组学分析声创伤后大鼠的脑代谢变化，作为直接将代谢变化与耳鸣联系起来之前的试点研究。使用基于气相色谱/质谱（GC/MS）的代谢组学平台分析了从假手术或声创伤动物中收集的12个不同脑区中的代谢产物。在质谱解卷积和分子鉴定后，使用多变量统计分析处理代谢组学数据。主成分分析表明，不同脑区的代谢模式不同，但功能相似的脑区有相似的代谢物组成。声损伤并没有改变这些地区的代谢物集群。当使用正交投影到潜在结构判别分析子模型在每个脑区域内进行分析时，在听觉皮层、下丘、上级丘、前庭核复合体（VNC）和小脑中，17种分子在对照组和声创伤组之间显示出明显的分离。进一步的代谢途径影响分析和富集概述与网络分析表明，氨基酸代谢的主要参与，包括丙氨酸，天冬氨酸和谷氨酸代谢途径，精氨酸和脯氨酸代谢途径和嘌呤代谢途径。我们的研究结果提供了第一个代谢组学证据，声损伤可以引起多种代谢途径的变化。这项初步研究还表明，代谢组学方法有可能在未来的研究中识别声创伤特异性代谢变化，其中代谢变化与动物的耳鸣状态相关。
Acoustic trauma is the most common cause of hearing loss and tinnitus in humans. However, the impact of acoustic trauma on system biology is not fully understood. It has been increasingly recognized that tinnitus caused by acoustic trauma is unlikely to be generated by a single pathological source, but rather a complex network of changes involving not only the auditory system but also systems related to memory, emotion and stress. One obvious and significant gap in tinnitus research is a lack of biomarkers that reflect the consequences of this interactive “tinnitus-causing” network. In this study, we made the first attempt to analyse brain metabolic changes in rats following acoustic trauma using metabolomics, as a pilot study prior to directly linking metabolic changes to tinnitus. Metabolites in 12 different brain regions collected from either sham or acoustic trauma animals were profiled using a gas chromatography mass spectrometry (GC/MS)-based metabolomics platform. After deconvolution of mass spectra and identification of the molecules, the metabolomic data were processed using multivariate statistical analysis. Principal component analysis showed that metabolic patterns varied among different brain regions; however, brain regions with similar functions had a similar metabolite composition. Acoustic trauma did not change the metabolite clusters in these regions. When analyzed within each brain region using the orthogonal projection to latent structures discriminant analysis sub-model, 17 molecules showed distinct separation between control and acoustic trauma groups in the auditory cortex, inferior colliculus, superior colliculus, vestibular nucleus complex (VNC), and cerebellum. Further metabolic pathway impact analysis and the enrichment overview with network analysis suggested the primary involvement of amino acid metabolism, including the alanine, aspartate and glutamate metabolic pathways, the arginine and proline metabolic pathways and the purine metabolic pathway. Our results provide the first metabolomics evidence that acoustic trauma can induce changes in multiple metabolic pathways. This pilot study also suggests that the metabolomic approach has the potential to identify acoustic trauma-specific metabolic shifts in future studies where metabolic changes are correlated with the animal's tinnitus status.