Gross Johann, Knipper Marlies, Mazurek Birgit
Tinnitus Center, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
Leibniz Society of Science Berlin, 10117 Berlin, Germany.
Int J Mol Sci. 2025 Feb 20;26(5):1831. doi: 10.3390/ijms26051831.
Proteins involved in synaptic transmission in normal hearing, acoustic stimulation, and tinnitus were identified using protein-protein interaction (PPI) networks. The gene list for tinnitus was compiled from the GeneCards database using the keywords "synaptic transmission" AND "inferior colliculus" AND "tinnitus" (Tin). For comparison, two gene lists were built using the keywords "auditory perception" (AP) and "acoustic stimulation" (AS). The STRING and the Cytoscape data analyzer were used to identify the top two high-degree proteins (HDPs) and the corresponding high-score interaction proteins (HSIP). The top1 key proteins of the AP and AS processes are BDNF and the receptor NTRK2; the top2 key proteins in the AP process are PVALB, together with GAD1, CALB1, and CALB2, which are important for the balance of excitation and inhibition. In the AS process, the top2 key proteins are FOS, CREB1, EGR1, and MAPK1, reflecting an activated state. The top1 key proteins of the Tin process are BDNF, NTRK3, and NTF3; these proteins are associated with the proliferation and differentiation of neurons and indicate the remodeling of synaptic transmission in IC. The top2 key proteins are GFAP and S100B, indicating a role for astrocytes in the modulation of synaptic transmission.
利用蛋白质-蛋白质相互作用（PPI）网络鉴定了正常听力、听觉刺激和耳鸣中涉及突触传递的蛋白质。耳鸣的基因列表是使用关键词“突触传递”、“下丘”和“耳鸣”（Tin）从GeneCards数据库中汇编而成。为了进行比较，使用关键词“听觉感知”（AP）和“听觉刺激”（AS）构建了两个基因列表。使用STRING和Cytoscape数据分析器来鉴定前两个高度蛋白质（HDPs）和相应的高分相互作用蛋白质（HSIP）。AP和AS过程的首要关键蛋白是脑源性神经营养因子（BDNF）和受体神经营养酪氨酸激酶2（NTRK2）；AP过程中的第二关键蛋白是小白蛋白（PVALB），以及对兴奋和抑制平衡很重要的谷氨酸脱羧酶1（GAD1）、钙结合蛋白1（CALB1）和钙结合蛋白2（CALB2）。在AS过程中，第二关键蛋白是原癌基因蛋白FOS、环磷腺苷效应元件结合蛋白1（CREB1）、早期生长反应蛋白1（EGR1）和丝裂原活化蛋白激酶1（MAPK1），反映了一种激活状态。耳鸣过程的首要关键蛋白是BDNF、神经营养酪氨酸激酶3（NTRK3）和神经营养因子3（NTF3）；这些蛋白质与神经元的增殖和分化相关，并表明下丘中突触传递的重塑。第二关键蛋白是胶质纤维酸性蛋白（GFAP）和S100B蛋白，表明星形胶质细胞在突触传递调节中发挥作用。
