ENT Institute and Department of Otorhinolaryngology, EYE & ENT Hospital, Fudan University, Shanghai, 200031, China.
NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai, 200031, China.
Adv Sci (Weinh). 2024 Jan;11(3):e2304709. doi: 10.1002/advs.202304709. Epub 2023 Nov 27.
Compared with individuals with hearing loss, tinnitus patients without hearing loss have more psychological or emotional problems. Tinnitus is closely associated to abnormal metabolism and function of the limbic system, a key brain region for emotion experience, but the underlying molecular mechanism remains unknown. Using whole-brain microvasculature dynamics imaging, the anterior cingulate cortex (ACC) is identified as a key brain region of limbic system involve in the onset of salicylate-induced tinnitus in mice. In the tinnitus group, there is enhanced purine metabolism, oxidative phosphorylation, and a distinct pattern of phosphorylation in glutamatergic synaptic pathway according to the metabolome profiles, quantitative proteomic, and phosphoproteomic data of mice ACC tissue. Electroencephalogram in tinnitus patients with normal hearing thresholds show that the functional connectivity between pregenual anterior cingulate cortex and the primary auditory cortex is significantly increased for high-gamma frequency band, which is positively correlated with the serum glutamate level. These findings indicate that ACC plays an important role in the pathophysiology of tinnitus by interacting with the primary auditory cortex and provide potential molecular targets in the ACC for tinnitus treatment.
与听力损失个体相比，无听力损失的耳鸣患者有更多的心理或情绪问题。耳鸣与边缘系统（情绪体验的关键大脑区域）的代谢和功能异常密切相关，但潜在的分子机制尚不清楚。使用全脑微血管动力学成像，发现扣带前皮质（ACC）是参与水杨酸诱导的小鼠耳鸣发作的边缘系统关键脑区。在耳鸣组中，根据代谢组学、定量蛋白质组学和小鼠 ACC 组织的磷酸化蛋白质组学数据，发现嘌呤代谢、氧化磷酸化增强，谷氨酸能突触通路的磷酸化模式明显。正常听力阈值的耳鸣患者的脑电图显示，前扣带皮质和初级听觉皮层之间的高频带功能连接显著增加，与血清谷氨酸水平呈正相关。这些发现表明，ACC 通过与初级听觉皮层相互作用在耳鸣的病理生理学中起重要作用，并为 ACC 中的耳鸣治疗提供了潜在的分子靶点。
