Mun Seog-Kyun, Chae Hyunkyu, Piao Xian-Yu, Lee Hyun-Jin, Kim Young-Kook, Oh Seung-Ha, Chang Munyoung
Department of Otorhinolaryngology-Head and Neck Surgery, Chung-Ang University College of Medicine, Seoul, Korea.
Department of Otorhinolaryngology, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwon, Korea.
Clin Exp Otorhinolaryngol. 2021 Feb;14(1):76-81. doi: 10.21053/ceo.2019.01382. Epub 2020 Jul 11.
Our research group has previously demonstrated that hearing loss might be a risk factor for synaptic loss within the hippocampus and impairment of cognition using an animal model of Alzheimer disease. In this study, after inducing hearing loss in a rat model of Alzheimer disease, the associations of various microRNAs (miRNAs) with cognitive impairment were investigated.
Rats were divided randomly into two experimental groups: the control group, which underwent sham surgery and subthreshold amyloid-β infusion and the deaf group, which underwent bilateral cochlear ablation and subthreshold amyloid-β infusion. All rats completed several cognitive function assessments 11 weeks after surgery, including the object-in-place task (OPT), the novel object recognition task (NOR), the object location task (OLT), and the Y-maze test. After the rats completed these tests, hippocampus tissue samples were assessed using miRNA microarrays. Candidate miRNAs were selected based on the results and then validated with quantitative reverse transcriptionpolymerase chain reaction (qRT-PCR) analyses.
The deaf group showed considerably lower scores on the OPT, OLT, and Y-maze test than the control group. The microarray analysis revealed that miR-29b-3p, -30e-5p, -153-3p, -376a-3p, -598-3p, -652-5p, and -873-3p were candidate miRNAs, and qRT-PCR showed significantly higher levels of miR-376a-3p and miR-598-3p in the deaf group.
These results indicate that miR-376a-3p and miR-598-3p were related to cognitive impairment after hearing loss.
我们的研究小组先前已证明，使用阿尔茨海默病动物模型，听力损失可能是海马体内突触损失和认知障碍的一个风险因素。在本研究中，在阿尔茨海默病大鼠模型中诱导听力损失后，研究了各种微小RNA（miRNA）与认知障碍的关联。
将大鼠随机分为两个实验组：对照组，接受假手术和亚阈值淀粉样β蛋白注入；耳聋组，接受双侧耳蜗切除和亚阈值淀粉样β蛋白注入。所有大鼠在手术后11周完成了多项认知功能评估，包括原地物体任务（OPT）、新物体识别任务（NOR）、物体定位任务（OLT）和Y迷宫测试。大鼠完成这些测试后，使用miRNA微阵列评估海马组织样本。根据结果选择候选miRNA，然后通过定量逆转录聚合酶链反应（qRT-PCR）分析进行验证。
耳聋组在OPT、OLT和Y迷宫测试中的得分明显低于对照组。微阵列分析显示，miR-29b-3p、-30e-5p、-153-3p、-376a-3p、-598-3p、-652-5p和-873-3p是候选miRNA，qRT-PCR显示耳聋组中miR-376a-3p和miR-598-3p的水平显著更高。
这些结果表明，miR-376a-3p和miR-598-3p与听力损失后的认知障碍有关。
