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

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

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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, beside the well described L-VGCC CaV1.3, also CaV1.2 is expressed. Due to lethality of constitutive CaV1.2 KO 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 (SGN), dorsal cochlear nucleus (DCN), and inferior colliculus (IC). 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 (ABR) 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.

Original languageEnglish (US)
JournalFrontiers in Molecular Neuroscience
Issue numberJULY
DOIs
StatePublished - Jul 20 2013

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Cochlea
Brain-Derived Neurotrophic Factor
Brain Stem
Noise
Inner Auditory Hair Cells
Spiral Ganglion
Cochlear Nucleus
Inferior Colliculi
Cochlear Nerve
Auditory Cortex
Brain Stem Auditory Evoked Potentials
Inner Ear
Ion Channels
Nerve Fibers
Hearing Loss
Hearing
Maintenance
Neurons
Messenger RNA
Peptides

Keywords

  • ABR
  • BDNF
  • Ca1.2
  • Inner ear
  • L-VGCCs
  • SOC

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Molecular Biology

Cite this

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. / Zuccotti, Annalisa; Lee, Sze Chim; Campanelli, Dario; Singer, Wibke; Satheesh, Somisetty Venkata; Patriarchi, Tommaso; Geisler, Hyun Soon; Köpschall, Iris; Rohbock, Karin; Nothwang, Hans Gerd; Hu, Jing; Hell, Johannes W; Schimmang, Thomas; Rüttiger, Lukas; Knipper, Marlies.

In: Frontiers in Molecular Neuroscience, No. JULY, 20.07.2013.

Research output: Contribution to journalArticle

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 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, no. JULY. https://doi.org/10.3389/fnmol.2013.00020
Zuccotti, Annalisa ; Lee, Sze Chim ; Campanelli, Dario ; Singer, Wibke ; Satheesh, Somisetty Venkata ; Patriarchi, Tommaso ; Geisler, Hyun Soon ; Köpschall, Iris ; Rohbock, Karin ; Nothwang, Hans Gerd ; Hu, Jing ; Hell, Johannes W ; Schimmang, Thomas ; Rüttiger, Lukas ; Knipper, Marlies. / 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. In: Frontiers in Molecular Neuroscience. 2013 ; No. JULY.
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T2 - Implication for CaV1.2 mediated control of cochlear BDNF expression

AU - Zuccotti, Annalisa

AU - Lee, Sze Chim

AU - Campanelli, Dario

AU - Singer, Wibke

AU - Satheesh, Somisetty Venkata

AU - Patriarchi, Tommaso

AU - Geisler, Hyun Soon

AU - Köpschall, Iris

AU - Rohbock, Karin

AU - Nothwang, Hans Gerd

AU - Hu, Jing

AU - Hell, Johannes W

AU - Schimmang, Thomas

AU - Rüttiger, Lukas

AU - Knipper, Marlies

PY - 2013/7/20

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N2 - 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, beside the well described L-VGCC CaV1.3, also CaV1.2 is expressed. Due to lethality of constitutive CaV1.2 KO 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 (SGN), dorsal cochlear nucleus (DCN), and inferior colliculus (IC). 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 (ABR) 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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