Ruan Qingwei, Yu Zhuowei, Zhang Weibin, Ruan Jian, Liu Chunhui, Zhang Ruxin
Shanghai Institute of Geriatrics and Gerontology, Shanghai Key Laboratory of Clinical Geriatrics, Huadong Hospital, and Research Center of Aging and Medicine, Shanghai Medical College, Fudan University, Shanghai, China.
Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Aging Neurosci. 2018 Apr 6;10:98. doi: 10.3389/fnagi.2018.00098. eCollection 2018.
Presbycusis (age-related hearing loss) is a potential risk factor for tinnitus and cognitive deterioration, which result in poor life quality. Presbycusis-related tinnitus with cognitive impairment is a common phenotype in the elderly population. In these individuals, the central auditory system shows similar pathophysiological alterations as those observed in Alzheimer's disease (AD), including cholinergic hypofunction, epileptiform-like network synchronization, chronic inflammation, and reduced GABAergic inhibition and neural plasticity. Observations from experimental rodent models indicate that recovery of cholinergic function can improve memory and other cognitive functions via acetylcholine-mediated GABAergic inhibition enhancement, nicotinic acetylcholine receptor (nAChR)-mediated anti-inflammation, glial activation inhibition and neurovascular protection. The loss of cholinergic innervation of various brain structures may provide a common link between tinnitus seen in presbycusis-related tinnitus and age-related cognitive impairment. We hypothesize a key component of the condition is the withdrawal of cholinergic input to a subtype of GABAergic inhibitory interneuron, neuropeptide Y (NPY) neurogliaform cells. Cholinergic denervation might not only cause the degeneration of NPY neurogliaform cells, but may also result in decreased AChR activation in GABAergic inhibitory interneurons. This, in turn, would lead to reduced GABA release and inhibitory regulation of neural networks. Reduced nAChR-mediated anti-inflammation due to the loss of nicotinic innervation might lead to the transformation of glial cells and release of inflammatory mediators, lowering the buffering of extracellular potassium and glutamate metabolism. Further research will provide evidence for the recovery of cholinergic function with the use of cholinergic input enhancement alone or in combination with other rehabilitative interventions to reestablish inhibitory regulation mechanisms of involved neural networks for presbycusis-related tinnitus with cognitive impairment.
老年性聋（年龄相关性听力损失）是耳鸣和认知功能减退的潜在危险因素，这会导致生活质量下降。伴有认知障碍的老年性聋相关性耳鸣是老年人群中的常见表型。在这些个体中，中枢听觉系统表现出与阿尔茨海默病（AD）中观察到的类似病理生理改变，包括胆碱能功能减退、癫痫样网络同步、慢性炎症以及γ-氨基丁酸（GABA）能抑制和神经可塑性降低。来自实验性啮齿动物模型的观察表明，胆碱能功能的恢复可通过乙酰胆碱介导的GABA能抑制增强、烟碱型乙酰胆碱受体（nAChR）介导的抗炎作用、胶质细胞激活抑制和神经血管保护来改善记忆和其他认知功能。各种脑结构胆碱能神经支配的丧失可能为老年性聋相关性耳鸣中出现的耳鸣与年龄相关性认知障碍之间提供一个共同联系。我们假设该病症的一个关键因素是胆碱能输入从一种GABA能抑制性中间神经元亚型——神经肽Y（NPY）神经胶质样细胞撤回。胆碱能去神经支配不仅可能导致NPY神经胶质样细胞退化，还可能导致GABA能抑制性中间神经元中AChR激活减少。反过来，这将导致GABA释放减少和神经网络的抑制调节减弱。由于烟碱型神经支配丧失导致的nAChR介导的抗炎作用减弱可能会导致胶质细胞转化和炎症介质释放，降低细胞外钾的缓冲能力和谷氨酸代谢。进一步的研究将为单独使用胆碱能输入增强或与其他康复干预措施联合使用以恢复胆碱能功能提供证据，从而为伴有认知障碍的老年性聋相关性耳鸣重新建立相关神经网络的抑制调节机制。
