Cdh23^(erl2/erl2)小鼠年龄相关性听力损失与认知障碍相关性的研究  

Correlation between Age-related Hearing Loss and Cognitive Dysfunction in Cdh23^(erl2/erl2) Mice

作　　者：吴远程 唐丽欢 谢道莉 郑体花[1] 王晓雯 郑庆印[1] 李博[1] WU Yuancheng;TANG Lihuan;XIE Daoli;ZHENG Tihua;WANG Xiaowen;ZHENG Qingyin;LI Bo(Hearing and Speech Rehabilitation Institute,school of Special Education and Rehabilitation,Binzhou Medical University,Yantai 264003,China)

机构地区：[1]滨州医学院特殊教育与康复学院听力与言语康复研究院,烟台264003

出　　处：《中华耳科学杂志》2024年第6期989-995,共7页Chinese Journal of Otology

基　　金：国家自然科学基金-面上项目(82371137);国家自然科学基金-重点项目(81530030);山东省优质专业学位教学案例库(SDYAL2022186);滨州医学院教学改革与研究项目(JYKTMP2021013);滨州医学院大学生创新创业训练项目(202310440183);山东省研究生优质课程(SDYKC2023184);山东省自然科学基金面上项目(ZR2014MH263)。

摘　　要：目的利用Cdh23^(erl2/erl2)(Erl2)小鼠模型来研究年龄相关性听力损失与认知功能障碍相关性。方法将Erl2小鼠和CBA/CaJ背景鼠分为2月龄组,4月龄组和8月龄组。利用听性脑干反应(auditory brainstem response,ABR)测试小鼠听力;行为学实验(新物体识别实验、Y迷宫实验和Morris水迷宫实验)用于评估小鼠的认知功能;对小鼠听力阈值与行为学实验结果进行Pearson相关性分析,以评估年龄相关性听力损失和认知功能障碍的相关性;利用免疫荧光实验观察小鼠海马体齿状回的新生神经元。结果听力功能检测显示Erl2小鼠随年龄增长听力阈值升高,呈现年龄相关性听力损失。CBA/CaJ小鼠随年龄增长听力无明显改变。行为学实验:新物体识别实验、Y迷宫实验和Morris水迷宫实验均提示,相比于CBA/CaJ小鼠,8月龄的Erl2小鼠认知功能下降,而2月龄和4月龄的两种小鼠在行为学上没有表现出差异。相关性分析结果:Erl2小鼠的年龄相关性听力损失和行为学实验结果存在相关性。免疫荧光实验:8月龄的Erl2小鼠海马齿状回的新生神经元数量明显少于CBA/CaJ小鼠。结论Erl2小鼠年龄相关性听力损失和认知功能下降存在相关性。海马体齿状回神经元再生减少可能是Erl2小鼠年龄相关性听力损失和认知能力下降相关联的病理机制之一。Objective To study the correlation between age-related hearing loss and cognitive dysfunction using the Erl2 mouse model.Methods Erl2 and CBA/CaJ mice were grouped based on age(2,4 and 8 months).Auditory brain stem responses(ABRs)were used to assess auditory function,and novel object recognition,the Y-maze and Morris water maze tests were used to assess cognitive function.Pearson analysis was used to determine correlation between age-related hearing loss and cognitive decline.Immunofluorescence assay was used to label neonatal neurons in the dentate gyrus of the hippocampus.Results ABR thresholds in Erl2 mice increased with age,showing agerelated hearing loss,but not in CBA/CaJ mice.Compared with CBA/CaJ mice,novel object recognition,Y maze and Morris water maze measurements all decreased in 8-months-old Erl2 mice,but not in 2-and 4-months-old mice.There was a correlation between age-related hearing loss and cognitive decline in Erl2 mice.Immunofluorescence showed significantly lower numbers of neonatal neurons in the dentate gyrus region of the hippocampus in 8-month-old Erl2 mice than in CBA/CaJ mice.Conclusion There was a correlation between age-related hearing loss and cognitive decline in Erl2 mice.Reduced neuron regeneration in the dentate gyrus of hippocampus may be one of the pathologic mechanisms associated with age-related hearing loss and cognitive decline.

关 键 词：年龄相关性听力损失 认知功能障碍 海马 

分 类 号：R764.43[医药卫生—耳鼻咽喉科]