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两孔通道(TPC)突变小鼠中意外的母性引发的听力损失

Unexpected Motherhood-Triggered Hearing Loss in the Two-Pore Channel (TPC) Mutant Mouse.

作者信息

Royer Juliette, Cancela José-Manuel, Edeline Jean-Marc

机构信息

Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Saclay, CNRS, Centre CEA Paris-Saclay-bât 151, 91400 Saclay, France.

出版信息

Biomedicines. 2022 Jul 15;10(7):1708. doi: 10.3390/biomedicines10071708.

DOI:10.3390/biomedicines10071708
PMID:35885013
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9312904/
Abstract

Calcium signaling is crucial for many physiological processes and can mobilize intracellular calcium stores in response to environmental sensory stimuli. The endolysosomal two-pore channel (TPC), regulated by the second messenger nicotinic acid adenine dinucleotide phosphate (NAADP), is one of the key components in calcium signaling. However, its role in neuronal physiology remains largely unknown. Here, we investigated to what extent the acoustic thresholds differed between the WT mice and the TPC KO mice. We determined the thresholds based on the auditory brainstem responses (ABRs) at five frequencies (between 4 and 32 kHz) and found no threshold difference between the WT and KO in virgin female mice. Surprisingly, in lactating mothers (at P9-P10), the thresholds were higher from 8 to 32 kHz in the TPC KO mice compared to the WT mice. This result indicates that in the TPC KO mice, physiological events occurring during parturition altered the detection of sounds already at the brainstem level, or even earlier.

摘要

钙信号传导对许多生理过程至关重要,并且能够响应环境感官刺激而动员细胞内钙库。由第二信使烟酰胺腺嘌呤二核苷酸磷酸(NAADP)调节的内溶酶体双孔通道(TPC)是钙信号传导的关键组成部分之一。然而,其在神经元生理学中的作用仍 largely 未知。在这里,我们研究了野生型小鼠和 TPC 基因敲除小鼠之间的听觉阈值差异程度。我们基于五个频率(4 至 32 kHz 之间)的听觉脑干反应(ABR)确定了阈值,发现未生育雌性小鼠的野生型和基因敲除型之间没有阈值差异。令人惊讶的是,在哺乳期母亲(产后 9 - 10 天)中,与野生型小鼠相比,TPC 基因敲除小鼠在 8 至 32 kHz 的阈值更高。这一结果表明,在 TPC 基因敲除小鼠中,分娩期间发生的生理事件在脑干水平甚至更早阶段就改变了声音的检测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6596/9312904/2ba428f0b9bc/biomedicines-10-01708-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6596/9312904/6445de54c583/biomedicines-10-01708-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6596/9312904/82c1932cb0ae/biomedicines-10-01708-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6596/9312904/2ba428f0b9bc/biomedicines-10-01708-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6596/9312904/6445de54c583/biomedicines-10-01708-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6596/9312904/82c1932cb0ae/biomedicines-10-01708-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6596/9312904/2ba428f0b9bc/biomedicines-10-01708-g003.jpg

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Neurophysiological functions and pharmacological tools of acidic and non-acidic Ca stores.酸和非酸性钙库的神经生理学功能和药理学工具。
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Mutation of SLC7A14 causes auditory neuropathy and retinitis pigmentosa mediated by lysosomal dysfunction.SLC7A14 突变导致溶酶体功能障碍介导的听觉神经病和视网膜色素变性。
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Acidic Ca stores and immune-cell function.酸性钙库与免疫细胞功能。
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Does pregnancy have an influence on otosclerosis?妊娠是否会对耳硬化症产生影响?
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Temporal Alterations to Central Auditory Processing without Synaptopathy after Lifetime Exposure to Environmental Noise.终身暴露于环境噪声后,中枢听觉处理无突触病变的时间性改变。
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CCDC154 Mutant Caused Abnormal Remodeling of the Otic Capsule and Hearing Loss in Mice.CCDC154突变导致小鼠耳囊异常重塑及听力损失
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