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听力损失小鼠的认知能力下降及海马体p-tau蛋白表达增加。

Cognitive decline and increased hippocampal p-tau expression in mice with hearing loss.

作者信息

Park So Young, Kim Min Jung, Kim Hong Lim, Kim Dong Kee, Yeo Sang Won, Park Shi Nae

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Integrative Research Support Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

出版信息

Behav Brain Res. 2018 Apr 16;342:19-26. doi: 10.1016/j.bbr.2018.01.003. Epub 2018 Jan 6.

DOI:10.1016/j.bbr.2018.01.003
PMID:29317248
Abstract

Hearing and cognition are commonly involved in both normal and pathological aging. Current clinical interest lies in whether peripheral hearing loss promotes cognitive decline. In our previous publication, the authors have shown a causal relationship between hearing and cognitive impairments in C57BL/6 mice. Here we extended the follow-up to 12 months to determine the long-term effects of hearing loss on cognition and to observe hippocampal p-tau and lipofuscin. One month old male mice were randomly allocated into two groups, the control (n = 12) and noise-induced hearing loss (NIHL) (n = 12). After baseline hearing and cognitive measurements, the mice in the NIHL group were exposed to 110 dB SPL white noise for 1 h every day for 20 consecutive days. Cognitive function was assessed by radial arm maze and novel object recognition tests. p-Tau was observed by the western blot, immunofluorescence, and immunogold staining. The mice in the NIHL group showed elevated auditory brainstem response thresholds and poorer performances in spatial working and recognition memories than the controls. They exhibited more p-tau and lipofuscin in the hippocampus. The cognitive impact of hearing loss varied with the types of memory. Working memory impairment was reversible, whereas recognition memory impairment was permanent. Our results provide behavioral and histopathological evidence for hearing-related cognitive decline. Early hearing loss is suggested to be one of the important determinants between normal and pathological cognitive aging.

摘要

听力和认知在正常衰老和病理性衰老过程中通常都会受到影响。目前临床关注的是外周性听力损失是否会促进认知能力下降。在我们之前发表的文章中,作者已经证明了C57BL/6小鼠的听力与认知障碍之间存在因果关系。在此,我们将随访时间延长至12个月,以确定听力损失对认知的长期影响,并观察海马体中的磷酸化tau蛋白和脂褐素。将1月龄雄性小鼠随机分为两组,即对照组(n = 12)和噪声性听力损失组(NIHL)(n = 12)。在进行基线听力和认知测量后,NIHL组的小鼠连续20天每天暴露于110 dB SPL的白噪声中1小时。通过放射状臂迷宫和新物体识别测试评估认知功能。通过蛋白质免疫印迹法、免疫荧光法和免疫金染色法观察磷酸化tau蛋白。NIHL组的小鼠听觉脑干反应阈值升高,在空间工作记忆和识别记忆方面的表现比对照组差。它们在海马体中表现出更多的磷酸化tau蛋白和脂褐素。听力损失对认知的影响因记忆类型而异。工作记忆障碍是可逆的,而识别记忆障碍是永久性的。我们的研究结果为听力相关的认知衰退提供了行为学和组织病理学证据。早期听力损失被认为是正常认知衰老和病理性认知衰老之间的重要决定因素之一。

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