Salicylate alters the expression of calcium response transcription factor 1 in the cochlea: implications for brain-derived neurotrophic factor transcriptional regulation

Molecular Pharmacology
Wibke SingerMarlies Knipper

Abstract

Brain-derived neurotrophic factor (BDNF) is a key neurotrophin whose expression is altered in response to neurological activity, influencing both short- and long-term synaptic changes. The BDNF gene consists of eight upstream exons (I-VII), each of which has a distinct promoter and can be independently spliced to the ninth coding exon (IX). We showed recently that the expression of BDNF exon IV in the cochlea is altered after exposure to salicylate, an ototoxic drug that in high doses is able to induce hearing loss and tinnitus. These changes were a crucial trigger for plasticity changes in the central auditory system. BDNF exon IV expression is regulated via interaction between calcium-response elements CaRE1, CaRE2, and CaRE3/Cre (CaREs) that are bound by the transcription factors CaRF1, upstream stimulatory factors 1 and 2 (USF1/2), and cAMP/Ca(2+) response element-binding protein (CREB), respectively. To determine whether the salicylate-induced changes in cochlear BDNF exon IV expression include a differential use of the CaRE binding proteins, we studied the level of the corresponding binding proteins in the spiral ganglion neurons before and after systemic application of concentrated salicylate using in situ hybridization ...Continue Reading

References

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Citations

May 27, 2011·Cellular and Molecular Neurobiology·Johann GrossBirgit Mazurek
Apr 22, 2010·Neurological Research·Daniel E NoyolaGail J Demmler-Harrison
Aug 10, 2010·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Fabio FumagalliMarco Andrea Riva
Aug 5, 2009·Hearing Research·Marlies KnipperMarcus Müller
Oct 10, 2012·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Steven H GreenRobin L Davis
May 22, 2013·Neuropharmacology·Wibke SingerMarlies Knipper
Apr 27, 2010·Pharmaceuticals·Tomofumi HoshinoAkira Hara
Jan 18, 2018·Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology·Bin YiHao Wu

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