Gross Johann, Knipper Marlies, Mazurek Birgit
Tinnitus Center, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
Leibniz Society of Sciences Berlin, 10117 Berlin, Germany.
Int J Mol Sci. 2025 Jun 17;26(12):5804. doi: 10.3390/ijms26125804.
To determine candidate key proteins involved in synaptic transmission in the thalamus in tinnitus, we used bioinformatic methods by analyzing protein-protein interaction networks under different conditions of acoustic activity. The motor system was used to analyze the specificity of the response reaction in the auditory system. The databases GeneCard, STRING-, DAVID-, and Cytoscape version 3.9.1 were applied to identify the top three high-degree proteins, their high-score interaction proteins and the gene ontology-biological processes (GO-BPs) associated in the thalamus with synaptic transmission in tinnitus. Under normal hearing conditions, a balanced state of functional connectivity was observed for both systems, the auditory system and the motor system of the thalamus. Under conditions of acoustic stimulation, the GO-BP-enrichment analyses suggest that in the auditory system, tinnitus-related proteins may be involved in responses typically associated with "xenobiotic stimuli"; in the motor system, the activation of the dopaminergic system was observed. Under conditions of tinnitus in the auditory system, key proteins and the GO-BPs indicate the regulation of different developmental processes and regulation by microRNA transcription; in the motor system, tinnitus is also identified as "xenobiotic" but responded with GO-BPs, corresponding to various signaling systems, e.g., tachykinin. Key proteins and their interactions with neurotransmitter receptors may be useful indicators for tinnitus-associated changes in synaptic transmission in the thalamic auditory system.
为了确定耳鸣时丘脑突触传递中涉及的候选关键蛋白,我们通过分析不同声学活动条件下的蛋白质-蛋白质相互作用网络,使用了生物信息学方法。利用运动系统来分析听觉系统中反应的特异性。应用GeneCard、STRING、DAVID和Cytoscape 3.9.1版本数据库来识别前三个高度蛋白、它们的高分相互作用蛋白以及丘脑与耳鸣突触传递相关的基因本体生物学过程(GO-BP)。在正常听力条件下,观察到丘脑的听觉系统和运动系统的功能连接处于平衡状态。在声学刺激条件下,GO-BP富集分析表明,在听觉系统中,耳鸣相关蛋白可能参与通常与“异源生物刺激”相关的反应;在运动系统中,观察到多巴胺能系统的激活。在听觉系统耳鸣条件下,关键蛋白和GO-BP表明不同发育过程的调节以及微小RNA转录的调节;在运动系统中,耳鸣也被识别为“异源生物”,但通过与各种信号系统(如速激肽)相对应的GO-BP做出反应。关键蛋白及其与神经递质受体的相互作用可能是丘脑听觉系统中与耳鸣相关的突触传递变化的有用指标。
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