PMID- 18524887
OWN - NLM
STAT- MEDLINE
DCOM- 20080918
LR  - 20131121
IS  - 1521-0111 (Electronic)
IS  - 0026-895X (Linking)
VI  - 74
IP  - 3
DP  - 2008 Sep
TI  - Midazolam reverses salicylate-induced changes in brain-derived neurotrophic 
      factor and arg3.1 expression: implications for tinnitus perception and auditory 
      plasticity.
PG  - 595-604
LID - 10.1124/mol.108.046375 [doi]
AB  - Tinnitus is a phantom auditory perception, which can be induced via application 
      of concentrated sodium salicylate, and is known to be associated with hearing 
      loss and altered neuronal excitability in peripheral and central auditory 
      neurons. The molecular features of this excitability, however, has been poorly 
      characterized to date. Brain-derived neurotrophic factor (BDNF), the 
      activity-dependent cytoskeletal protein (Arg3.1, also known as Arc), and c-Fos 
      are known to be affected by changes in excitability and plasticity. Using reverse 
      transcription-polymerase chain reaction, in situ hybridization, and 
      immunohistochemistry, the expression of these genes was monitored in the rat 
      auditory system after local (cochlear) and systemic application of salicylate. 
      Induction of tinnitus and hearing loss was verified in a behavioral model. 
      Regardless of the mode of salicylate application, a common pattern became 
      evident: 1) BDNF mRNA expression was increased in the spiral ganglion neurons of 
      the cochlea; and 2) Arg3.1 expression was significantly reduced in the auditory 
      cortex. Local application of the GABA(A) receptor modulator midazolam resulted in 
      the reversal not only of salicylate-induced changes in cochlear BDNF expression, 
      but also in cortical Arg3.1 expression, indicating that the tinnitus-associated 
      changes in cochlear BDNF expression trigger the decline of cortical Arg3.1 
      expression. Furthermore, local midazolam application reduced tinnitus perception 
      in the animal model. These findings support Arg3.1 and BDNF as markers for 
      activity changes in the auditory system and suggest a role of GABAergic 
      inhibition of cochlear neurons in the modulation of Arg3.1 plasticity changes in 
      the auditory cortex and tinnitus perception.
FAU - Panford-Walsh, Rama
AU  - Panford-Walsh R
AD  - Department of Otorhinolaryngology, Universitat Tubingen, Tubingen, Germany.
FAU - Singer, Wibke
AU  - Singer W
FAU - Ruttiger, Lukas
AU  - Ruttiger L
FAU - Hadjab, Saida
AU  - Hadjab S
FAU - Tan, Justin
AU  - Tan J
FAU - Geisler, Hyun-Soon
AU  - Geisler HS
FAU - Zimmermann, Ulrike
AU  - Zimmermann U
FAU - Kopschall, Iris
AU  - Kopschall I
FAU - Rohbock, Karin
AU  - Rohbock K
FAU - Vieljans, Anna
AU  - Vieljans A
FAU - Oestreicher, Elmar
AU  - Oestreicher E
FAU - Knipper, Marlies
AU  - Knipper M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080604
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, GABA)
RN  - 0 (Salicylates)
RN  - 0 (activity regulated cytoskeletal-associated protein)
RN  - R60L0SM5BC (Midazolam)
SB  - IM
MH  - Animals
MH  - Auditory Cortex/drug effects/metabolism
MH  - Auditory Pathways/drug effects/metabolism
MH  - Auditory Perception/*drug effects
MH  - Behavior, Animal/drug effects
MH  - Brain-Derived Neurotrophic Factor/*genetics/metabolism
MH  - Cochlea/drug effects/metabolism
MH  - Cytoskeletal Proteins/*genetics/metabolism
MH  - Female
MH  - Gene Expression Regulation/*drug effects
MH  - Hearing Loss/chemically induced
MH  - Midazolam/administration & dosage/*pharmacology
MH  - Models, Biological
MH  - Nerve Tissue Proteins/*genetics/metabolism
MH  - Neurons/cytology/drug effects/metabolism
MH  - Proto-Oncogene Proteins c-fos/genetics/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, GABA/metabolism
MH  - Salicylates/administration & dosage/*pharmacology
MH  - Tinnitus/*metabolism/pathology
EDAT- 2008/06/06 09:00
MHDA- 2008/09/19 09:00
CRDT- 2008/06/06 09:00
PHST- 2008/06/06 09:00 [pubmed]
PHST- 2008/09/19 09:00 [medline]
PHST- 2008/06/06 09:00 [entrez]
AID - mol.108.046375 [pii]
AID - 10.1124/mol.108.046375 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2008 Sep;74(3):595-604. doi: 10.1124/mol.108.046375. Epub 2008 Jun 
      4.