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阿尔茨海默病 5xFAD 小鼠模型中的 rod 通路和 cone 通路视网膜功能障碍。

Rod pathway and cone pathway retinal dysfunction in the 5xFAD mouse model of Alzheimer's disease.

机构信息

Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA.

Department of Ophthalmology, University of Southern California, Los Angeles, CA, USA.

出版信息

Sci Rep. 2021 Mar 1;11(1):4824. doi: 10.1038/s41598-021-84318-2.

DOI:10.1038/s41598-021-84318-2
PMID:33649406
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7921657/
Abstract

To characterize rod- and cone-pathway function in the 5xFAD mouse model of Alzheimer's disease (AD) using the full-field electroretinogram (ERG). Dark-adapted (DA; rod-pathway) and light-adapted (LA; cone-pathway) ERGs were recorded from three-month-old 5xFAD and wild type (WT) mice. ERGs were elicited by achromatic flashes (0.01-25 cd-s-m). Amplitude and implicit time (IT) of the a-wave, b-wave, and oscillatory potentials (OPs) were calculated according to convention. In addition, the amplitude and IT of the photopic negative response (PhNR) were measured from the LA recordings. Amplitude and IT differences between the 5xFAD and WT groups were evaluated using quantile regression models. Under DA conditions, there were significant differences between the 5xFAD and WT groups in post-receptor function, whereas photoreceptor function did not differ significantly. Specifically, the DA a-wave amplitude did not differ between groups (p = 0.87), whereas the b-wave amplitude was reduced in the 5xFAD mice (p = 0.003). There were significant OP (p < 0.001) and a-wave (p = 0.04) delays, but the a-wave delay may be attributable to a post-receptor abnormality. Under LA conditions, the only 5xFAD abnormalities were in the PhNR, which was reduced (p = 0.009) and delayed (p = 0.04). The full-field ERG can be abnormal in the 5xFAD model of AD, with the greatest effects on post-receptor rod pathway function. These results indicate that retinal electrophysiology may be a useful tool for evaluating neural dysfunction in AD.

摘要

使用全视野视网膜电图(ERG)描述阿尔茨海默病(AD)的 5xFAD 小鼠模型中的视杆和视锥通路功能。从 3 月龄的 5xFAD 和野生型(WT)小鼠中记录暗适应(DA;视杆通路)和明适应(LA;视锥通路)ERG。用非彩色闪光(0.01-25 cd-s-m)激发 ERG。根据惯例计算 a 波、b 波和眼震电图(OP)的振幅和潜伏期(IT)。此外,还从 LA 记录中测量光幻视负反应(PhNR)的振幅和 IT。使用分位数回归模型评估 5xFAD 和 WT 组之间的振幅和 IT 差异。在 DA 条件下,5xFAD 和 WT 组之间在后受体功能方面存在显著差异,而光感受器功能没有显著差异。具体而言,DA a 波振幅在两组之间没有差异(p=0.87),而 b 波振幅在 5xFAD 小鼠中降低(p=0.003)。存在显著的 OP(p<0.001)和 a 波(p=0.04)延迟,但 a 波延迟可能归因于后受体异常。在 LA 条件下,唯一的 5xFAD 异常是 PhNR,其降低(p=0.009)和延迟(p=0.04)。AD 的 5xFAD 模型中的全视野 ERG 可能异常,对视杆后通路功能的影响最大。这些结果表明视网膜电生理学可能是评估 AD 中神经功能障碍的有用工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2103/7921657/052f3b38d1da/41598_2021_84318_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2103/7921657/7332c480c499/41598_2021_84318_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2103/7921657/2304687099a8/41598_2021_84318_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2103/7921657/052f3b38d1da/41598_2021_84318_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2103/7921657/7332c480c499/41598_2021_84318_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2103/7921657/4dd7582eb53e/41598_2021_84318_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2103/7921657/4ee1b083aa8c/41598_2021_84318_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2103/7921657/2304687099a8/41598_2021_84318_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2103/7921657/052f3b38d1da/41598_2021_84318_Fig5_HTML.jpg

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