L-type CaV1.2 deletion in the cochlea but not in the brainstem reduces noise vulnerability: implication for CaV1.2-mediated control of cochlear BDNF expression.
L-type CaV1.2 deletion in the cochlea but not in the brainstem reduces noise vulnerability: implication for CaV1.2-mediated control of cochlear BDNF expression.
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DOI：
10.3389/fnmol.2013.00020
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发表时间：
2013
影响因子：
4.8
通讯作者：
Knipper M
中科院分区：
文献类型：
--
作者：
Zuccotti A;Lee SC;Campanelli D;Singer W;Satheesh SV;Patriarchi T;Geisler HS;Köpschall I;Rohbock K;Nothwang HG;Hu J;Hell JW;Schimmang T;Rüttiger L;Knipper M
电压门控L型钙通道（L-VGCC）如CaV1.2被认为在控制包括脑源性神经营养因子（BDNF）在内的营养肽的释放中起关键作用。在成年小鼠的内耳中，除了已充分描述的L-VGCC CaV 1.3外，还表达CaV 1.2。由于组成性CaV1.2基因敲除小鼠的致死性，该离子通道的功能以及其在听觉系统中与BDNF的推定关系是完全难以捉摸的。我们最近描述了BDNF在内毛细胞（IHC）囊泡在正常和创伤条件下的释放中起着不同的作用。为了阐明CaV1.2在此过程中的假定作用，产生了两个组织特异性条件小鼠系。为了区分CaV1.2对耳蜗的影响，从更高的听觉中心的反馈回路CaV1.2被删除，在一个小鼠行，在Pax 2启动子（CaV1.2Pax2），导致删除螺旋神经节神经元，耳蜗背核，下丘。在第二个小鼠系中，Egr 2启动子用于删除听觉脑干核中的CaV 1.2（CaV 1.2Egr 2）。在两种小鼠系中，观察到正常的听阈和相等数量的IHC释放位点。我们发现CaV1.2Pax2小鼠的听性脑干反应波I振幅略有降低，但CaV1.2Egr2小鼠没有。在噪声暴露后，CaV1.2Pax2小鼠的听力损失不太明显，这与IHC中条带的维持和听觉神经纤维的活动减少有关，以及在阈上声音刺激下的高级脑中心。由于在CaV1.2Pax2小鼠中发现耳蜗BDNF mRNA水平降低，我们认为CaV1.2依赖性步骤可能参与触发耳蜗BDNF在完整系统中的有益和恶化作用的一部分，并且在噪声暴露期间通过一种独立于CaV1.2传出回路功能的途径。
Voltage-gated L-type Ca2+ channels (L-VGCCs) like CaV1.2 are assumed to play a crucial role for controlling release of trophic peptides including brain-derived neurotrophic factor (BDNF). In the inner ear of the adult mouse, besides the well-described L-VGCC CaV1.3, CaV1.2 is also expressed. Due to lethality of constitutive CaV1.2 knock-out mice, the function of this ion channel as well as its putative relationship to BDNF in the auditory system is entirely elusive. We recently described that BDNF plays a differential role for inner hair cell (IHC) vesicles release in normal and traumatized condition. To elucidate a presumptive role of CaV1.2 during this process, two tissue-specific conditional mouse lines were generated. To distinguish the impact of CaV1.2 on the cochlea from that on feedback loops from higher auditory centers CaV1.2 was deleted, in one mouse line, under the Pax2 promoter (CaV1.2Pax2) leading to a deletion in the spiral ganglion neurons, dorsal cochlear nucleus, and inferior colliculus. In the second mouse line, the Egr2 promoter was used for deleting CaV1.2 (CaV1.2Egr2) in auditory brainstem nuclei. In both mouse lines, normal hearing threshold and equal number of IHC release sites were observed. We found a slight reduction of auditory brainstem response wave I amplitudes in the CaV1.2Pax2 mice, but not in the CaV1.2Egr2 mice. After noise exposure, CaV1.2Pax2 mice had less-pronounced hearing loss that correlated with maintenance of ribbons in IHCs and less reduced activity in auditory nerve fibers, as well as in higher brain centers at supra-threshold sound stimulation. As reduced cochlear BDNF mRNA levels were found in CaV1.2Pax2 mice, we suggest that a CaV1.2-dependent step may participate in triggering part of the beneficial and deteriorating effects of cochlear BDNF in intact systems and during noise exposure through a pathway that is independent of CaV1.2 function in efferent circuits.
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影响因子：
2.8
作者：
LIBERMAN, MC
通讯作者：
LIBERMAN, MC
DOI：
10.1523/jneurosci.1786-08.2008
发表时间：
2008-10-15
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Lubin FD;Roth TL;Sweatt JD
通讯作者：
Sweatt JD
DOI：
10.1523/jneurosci.2845-09.2009
发表时间：
2009-11-11
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kujawa SG;Liberman MC
通讯作者：
Liberman MC
影响因子：
2.9
作者：
El-Badry, Mohamed M.;McFadden, Sandra L.
通讯作者：
McFadden, Sandra L.
影响因子：
16.2
作者：
Barg, S;Olofsson, CS;Rorsman, P
通讯作者：
Rorsman, P