Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy.
Elife. 2021 Oct 26;10:e70908. doi: 10.7554/eLife.70908.
Although association between hearing impairment and dementia has been widely documented by epidemiological studies, the role of auditory sensory deprivation in cognitive decline remains to be fully understood. To address this issue we investigated the impact of hearing loss on the onset and time-course of cognitive decline in an animal model of Alzheimer's disease (AD), that is the 3×Tg-AD mice and the underlying mechanisms. We found that hearing loss induced by noise exposure in the 3×Tg-AD mice before the phenotype is manifested caused persistent synaptic and morphological alterations in the auditory cortex. This was associated with earlier hippocampal dysfunction, increased tau phosphorylation, neuroinflammation, and redox imbalance, along with anticipated memory deficits compared to the expected time-course of the neurodegenerative phenotype. Our data suggest that a mouse model of AD is more vulnerable to central damage induced by hearing loss and shows reduced ability to counteract noise-induced detrimental effects, which accelerates the neurodegenerative disease onset.
虽然流行病学研究广泛证明了听力损伤与痴呆之间的关联,但听觉感觉剥夺在认知能力下降中的作用仍有待充分理解。为了解决这个问题,我们研究了听力损失对阿尔茨海默病(AD)动物模型中认知能力下降的发生和时间进程的影响,即 3×Tg-AD 小鼠及其潜在机制。我们发现,在表型表现之前,噪声暴露引起的 3×Tg-AD 小鼠听力损失导致听觉皮层中持续的突触和形态改变。这与海马功能障碍更早、tau 磷酸化增加、神经炎症和氧化还原失衡以及预期记忆缺陷有关,与神经退行性表型的预期时间进程相比。我们的数据表明,AD 小鼠模型更容易受到听力损失引起的中枢损伤的影响,并且表现出降低的对抗噪声引起的有害影响的能力,这加速了神经退行性疾病的发生。