PMID- 23950737
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20130816
LR  - 20211021
IS  - 1662-5099 (Print)
IS  - 1662-5099 (Electronic)
IS  - 1662-5099 (Linking)
VI  - 6
DP  - 2013
TI  - 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.
PG  - 20
LID - 10.3389/fnmol.2013.00020 [doi]
LID - 20
AB  - 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.
FAU - Zuccotti, Annalisa
AU  - Zuccotti A
AD  - Molecular Physiology of Hearing, Hearing Research Center Tubingen, Department of 
      Otolaryngology, University of Tubingen Tubingen, Germany.
FAU - Lee, Sze C
AU  - Lee SC
FAU - Campanelli, Dario
AU  - Campanelli D
FAU - Singer, Wibke
AU  - Singer W
FAU - Satheesh, Somisetty V
AU  - Satheesh SV
FAU - Patriarchi, Tommaso
AU  - Patriarchi T
FAU - Geisler, Hyun-Soon
AU  - Geisler HS
FAU - Kopschall, Iris
AU  - Kopschall I
FAU - Rohbock, Karin
AU  - Rohbock K
FAU - Nothwang, Hans G
AU  - Nothwang HG
FAU - Hu, Jing
AU  - Hu J
FAU - Hell, Johannes W
AU  - Hell JW
FAU - Schimmang, Thomas
AU  - Schimmang T
FAU - Ruttiger, Lukas
AU  - Ruttiger L
FAU - Knipper, Marlies
AU  - Knipper M
LA  - eng
GR  - R01 AG017502/AG/NIA NIH HHS/United States
PT  - Journal Article
DEP - 20130809
PL  - Switzerland
TA  - Front Mol Neurosci
JT  - Frontiers in molecular neuroscience
JID - 101477914
PMC - PMC3739414
OTO - NOTNLM
OT  - ABR
OT  - BDNF
OT  - CaV1.2
OT  - L-VGCCs
OT  - SOC
OT  - inner ear
EDAT- 2013/08/21 06:00
MHDA- 2013/08/21 06:01
PMCR- 2013/01/01
CRDT- 2013/08/17 06:00
PHST- 2013/06/03 00:00 [received]
PHST- 2013/07/20 00:00 [accepted]
PHST- 2013/08/17 06:00 [entrez]
PHST- 2013/08/21 06:00 [pubmed]
PHST- 2013/08/21 06:01 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - 10.3389/fnmol.2013.00020 [doi]
PST - epublish
SO  - Front Mol Neurosci. 2013 Aug 9;6:20. doi: 10.3389/fnmol.2013.00020. eCollection 
      2013.