QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, July 16, 2008, 28(29):7313-7323; doi:10.1523/JNEUROSCI.5335-07.2008

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ruel, J. Articles by Puel, J.-L. PubMed PubMed Citation Articles by Ruel, J. Articles by Puel, J.-L. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB GLUTAMIC ACID HYDROCHLORIDE SALICYLIC ACID

 Previous Article  |  Next Article 

Cellular/Molecular
Salicylate Enables Cochlear Arachidonic-Acid-Sensitive NMDA Receptor Responses

Jérôme Ruel,^1,3 * Christian Chabbert,^1,3 * Régis Nouvian,^1,3 Rim Bendris,^1,3 Michel Eybalin,^1,3 Claude Louis Leger,² Jérôme Bourien,^1,3 Marcel Mersel,^1,3 and Jean-Luc Puel^1,3

¹Inserm, Unité Mixte de Recherche 583, F-34091 Montpellier, France, and ²Laboratoire de Nutrition Humaine et Athérogénése, ³Université Montpellier 1, F-34967 Montpellier, France

Correspondence should be addressed to Prof. Jean-Luc Puel, Inserm, Unité Mixte de Recherche 583, Institut des Neurosciences, 80 Avenue Augustin Fliche, F-34091 Montpellier cedex, France. Email: jean-luc.puel{at}inserm.fr

Currently, many millions of people treated for various ailments receive high doses of salicylate. Consequently, understanding the mechanisms by which salicylate induces tinnitus is an important issue for the research community. Behavioral testing in rats have shown that tinnitus induced by salicylate or mefenamate (both cyclooxygenase blockers) are mediated by cochlear NMDA receptors. Here we report that the synapses between the sensory inner hair cells and the dendrites of the cochlear spiral ganglion neurons express NMDA receptors. Patch-clamp recordings and two-photon calcium imaging demonstrated that salicylate and arachidonate (a substrate of cyclooxygenase) enabled the calcium flux and the neural excitatory effects of NMDA on cochlear spiral ganglion neurons. Salicylate also increased the arachidonate content of the whole cochlea in vivo. Single-unit recordings of auditory nerve fibers in adult guinea pig confirmed the neural excitatory effect of salicylate and the blockade of this effect by NMDA antagonist. These results suggest that salicylate inhibits cochlear cyclooxygenase, which increased levels of arachidonate. The increased levels of arachidonate then act on NMDA receptors to enable NMDA responses to glutamate that inner hair cells spontaneously release. This new pharmacological profile of salicylate provides a molecular mechanism for the generation of tinnitus at the periphery of the auditory system.

Key words: glutamate; salicylate; NMDA receptor; arachidonate; cochlea; tinnitus

---

Received Dec. 2, 2007; revised May 20, 2008; accepted May 20, 2008.

Correspondence should be addressed to Prof. Jean-Luc Puel, Inserm, Unité Mixte de Recherche 583, Institut des Neurosciences, 80 Avenue Augustin Fliche, F-34091 Montpellier cedex, France. Email: jean-luc.puel{at}inserm.fr

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help