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Zuccotti A, Lee SC, Campanelli D, et al. 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. Front Mol Neurosci. 2013;6:20doi: 10.3389/fnmol.2013.00020.
Zuccotti, A., Lee, S. C., Campanelli, D., Singer, W., Satheesh, S. V., Patriarchi, T., Geisler, H. S., Köpschall, I., Rohbock, K., Nothwang, H. G., Hu, J., Hell, J. W., Schimmang, T., Rüttiger, L., & Knipper, M. (2013). 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. Frontiers in molecular neuroscience, 620. https://doi.org/10.3389/fnmol.2013.00020
Zuccotti, Annalisa, et al. "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." Frontiers in molecular neuroscience vol. 6 (2013): 20. doi: https://doi.org/10.3389/fnmol.2013.00020
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. 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. Front Mol Neurosci. 2013 Aug 09;6:20. doi: 10.3389/fnmol.2013.00020. eCollection 2013. PMID: 23950737; PMCID: PMC3739414.
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Front Mol Neurosci. 2013 Aug 09;6:20. doi: 10.3389/fnmol.2013.00020. eCollection 2013.

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.

Frontiers in molecular neuroscience

Annalisa Zuccotti, Sze C Lee, Dario Campanelli, Wibke Singer, Somisetty V Satheesh, Tommaso Patriarchi, Hyun-Soon Geisler, Iris Köpschall, Karin Rohbock, Hans G Nothwang, Jing Hu, Johannes W Hell, Thomas Schimmang, Lukas Rüttiger, Marlies Knipper

Affiliations

  1. Molecular Physiology of Hearing, Hearing Research Center Tübingen, Department of Otolaryngology, University of Tübingen Tübingen, Germany.

PMID: 23950737 PMCID: PMC3739414 DOI: 10.3389/fnmol.2013.00020

Abstract

Voltage-gated L-type Ca(2+) 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 (CaV1.2(Pax2)) 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 (CaV1.2(Egr2)) 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 CaV1.2(Pax2) mice, but not in the CaV1.2(Egr2) mice. After noise exposure, CaV1.2(Pax2) 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 CaV1.2(Pax2) 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.

Keywords: ABR; BDNF; CaV1.2; L-VGCCs; SOC; inner ear

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