脆性X智力低下蛋白在听觉脑干突触发育中的自主作用研究

批准号:
32000697
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
王晓钰
依托单位:
学科分类:
感觉与运动系统神经生物学
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
王晓钰
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中文摘要
听觉脑干中,螺旋神经节细胞轴突末端与耳蜗核球形丛状细胞形成的海德氏终球(endbulb of Held, endbulb)可快速且高保真地传递听觉刺激,是传导性和感觉神经性听力损失的直接靶标,目前对endbulb的发育及病理机制仍知之甚少。脆性X智力低下蛋白(Fragile X mental retardation protein, FMRP)是一种mRNA结合蛋白,其缺失导致的脆性X综合征伴随听觉异常。我们的前期研究发现突触后神经元中FMRP缺乏导致endbulb发育异常,神经传递受损。假设FMRP在突触前后神经元及周围星形胶质细胞中具有不同的自主功能,在此项目中,我们将在endbulb发育的特定时间节点分别干扰突触前,突触后和星形胶质细胞中的FMRP水平,剖析突触不同组件间的相互作用及FMRP在endbulb形态发生,突触形成及功能成熟中的作用,为听觉研究及听力损伤疾病提供理论基础。
英文摘要
The spiral ganglion neurons connect the inner ear and spherical bushy cells in cochlear nucleus with endbulb of Held (endbulb), a large axosomatic synapse which allows ultra-fast and high-fidelity neurotransmission in auditory brainstem. As a gateway of auditory processing, endbulb is the target of both conductive and sensorineural hearing loss, however, little is known about the normal development and mechanisms of endbulb pathology. Fragile X mental retardation protein (FMRP) is an mRNA binding protein, loss of which leads to Fragile X syndrome characterized by intelligence disability and hearing deficits. Our previous study demonstrated the loss of postsynaptic FMRP results in altered endbulb morphology and compromised neurotransmission. Here, we hypothesize that the auditory nerve and postsynaptic bushy cells, as well as astrocytes, control different aspects of endbulb development through distinct signaling networks with FMRP as a critical regulator. In this study, we will dissect the autonomous function of FMRP during endbulb formation by respectively manipulating FMRP level in pre-, postsynaptic neurons and astrocytes in an age-specific manner. By investigating the interaction between synaptic components and the role of FMRP, we aim to provide further fundamental knowledge of auditory circuit wiring and the underlie mechanisms of hearing disfunction.
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DOI:10.1016/j.heares.2023.108720
发表时间:2023-02-19
期刊:HEARING RESEARCH
影响因子:2.8
作者:Wang,Xiaoyu;Sela-Donenfeld,Dalit;Wang,Yuan
通讯作者:Wang,Yuan
DOI:10.3791/64187-v
发表时间:2022
期刊:Journal of Visualized Experiments
影响因子:--
作者:Qiwei Fan;Xiaotan Zhang;Yuan Wang;Xiaoyu Wang
通讯作者:Xiaoyu Wang
脆性X智力低下蛋白FMRP在听觉环路频率拓扑发育中的作用研究
- 批准号:--
- 项目类别:面上项目
- 资助金额:52万元
- 批准年份:2022
- 负责人:王晓钰
- 依托单位:
脆性X智力低下蛋白(FMRP)在听觉耳蜗核轴突发育中的作用研究
- 批准号:--
- 项目类别:省市级项目
- 资助金额:10.0万元
- 批准年份:2021
- 负责人:王晓钰
- 依托单位:
国内基金
海外基金
