Tinnitus Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Leibniz Society of Science Berlin, Berlin, Germany.
Cell Mol Neurobiol. 2023 Nov;43(8):4189-4207. doi: 10.1007/s10571-023-01405-w. Epub 2023 Sep 22.
To study key proteins associated with changes in synaptic transmission in the spiral ganglion in tinnitus, we build three gene lists from the GeneCard database: 1. Perception of sound (PoS), 2. Acoustic stimulation (AcouStim), and 3. Tinnitus (Tin). Enrichment analysis by the DAVID database resulted in similar Gene Ontology (GO) terms for cellular components in all gene lists, reflecting synaptic structures known to be involved in auditory processing. The STRING protein-protein interaction (PPI) network and the Cytoscape data analyzer were used to identify the top two high-degree proteins (HDPs) and their high-score interaction proteins (HSIPs) identified by the combined score (CS) of the corresponding edges. The top two protein pairs (key proteins) for the PoS are BDNF-GDNF and OTOF-CACNA1D and for the AcouStim process BDNF-NTRK2 and TH-CALB1. The Tin process showed BDNF and NGF as HDPs, with high-score interactions with NTRK1 and NGFR at a comparable level. Compared to the PoS and AcouStim process, the number of HSIPs of key proteins (CS > 90. percentile) increases strongly in Tin. In the PoS and AcouStim networks, BDNF receptor signaling is the dominant pathway, and in the Tin network, the NGF-signaling pathway is of similar importance. Key proteins and their HSIPs are good indicators of biological processes and of signaling pathways characteristic for the normal hearing on the one hand and tinnitus on the other.
为了研究耳鸣中螺旋神经节突触传递变化相关的关键蛋白，我们从 GeneCard 数据库构建了三个基因列表：1. 声音感知（PoS），2. 声学刺激（AcouStim）和 3. 耳鸣（Tin）。DAVID 数据库的富集分析为所有基因列表的细胞成分提供了相似的基因本体（GO）术语，反映了已知参与听觉处理的突触结构。STRING 蛋白质-蛋白质相互作用（PPI）网络和 Cytoscape 数据分析器用于识别两个最高度蛋白（HDP）及其由相应边缘的组合得分（CS）识别的高得分相互作用蛋白（HSIP）。PoS 的两个最高蛋白对（关键蛋白）是 BDNF-GDNF 和 OTOF-CACNA1D，而 AcouStim 过程的是 BDNF-NTRK2 和 TH-CALB1。Tin 过程显示 BDNF 和 NGF 是 HDP，与 NTRK1 和 NGFR 的高得分相互作用水平相当。与 PoS 和 AcouStim 过程相比，Tin 中关键蛋白（CS > 90. 分位数）的 HSIP 数量大幅增加。在 PoS 和 AcouStim 网络中，BDNF 受体信号是主要途径，而在 Tin 网络中，NGF 信号途径具有相似的重要性。关键蛋白及其 HSIP 是正常听力和耳鸣特征的生物过程和信号通路的良好指标。
