RGD Reference Report - Midazolam reverses salicylate-induced changes in brain-derived neurotrophic factor and arg3.1 expression: implications for tinnitus perception and auditory plasticity. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Midazolam reverses salicylate-induced changes in brain-derived neurotrophic factor and arg3.1 expression: implications for tinnitus perception and auditory plasticity.

Authors: Panford-Walsh, R  Singer, W  Ruttiger, L  Hadjab, S  Tan, J  Geisler, HS  Zimmermann, U  Kopschall, I  Rohbock, K  Vieljans, A  Oestreicher, E  Knipper, M 
Citation: Panford-Walsh R, etal., Mol Pharmacol. 2008 Sep;74(3):595-604. doi: 10.1124/mol.108.046375. Epub 2008 Jun 4.
RGD ID: 8655535
Pubmed: PMID:18524887   (View Abstract at PubMed)
DOI: DOI:10.1124/mol.108.046375   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hearing Loss  ISOArc (Rattus norvegicus)8655535; 8655535mRNA:decreased expression:auditory cortex:RGD 
Hearing Loss  IEP 8655535mRNA:decreased expression:auditory cortex:RGD 
Hearing Loss  ISOBdnf (Rattus norvegicus)8655535; 8655535mRNA:increased expression:cochlea:RGD 
Hearing Loss  IEP 8655535mRNA:increased expression:cochlea:RGD 
Tinnitus  ISOArc (Rattus norvegicus)8655535; 8655535mRNA:decreased expression:auditory cortex:RGD 
Tinnitus  IEP 8655535mRNA:decreased expression:auditory cortex:RGD 
Tinnitus  ISOBdnf (Rattus norvegicus)8655535; 8655535mRNA:increased expression:cochlea:RGD 
Tinnitus  IEP 8655535mRNA:increased expression:cochlea:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Arc  (activity-regulated cytoskeleton-associated protein)
Bdnf  (brain-derived neurotrophic factor)

Genes (Mus musculus)
Arc  (activity regulated cytoskeletal-associated protein)
Bdnf  (brain derived neurotrophic factor)

Genes (Homo sapiens)
ARC  (activity regulated cytoskeleton associated protein)
BDNF  (brain derived neurotrophic factor)


Additional Information