Role of somatostatin receptor-2 in gentamicin-induced auditory hair cell loss in the Mammalian inner ear

Brand, Yves and Radojevic, Vesna and Sung, Michael and Wei, Eric and Setz, Cristian and Glutz, Andrea and Leitmeyer, Katharina and Bodmer, Daniel. (2014) Role of somatostatin receptor-2 in gentamicin-induced auditory hair cell loss in the Mammalian inner ear. PLoS ONE, 9 (9). e108146.

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Hair cells and spiral ganglion neurons of the mammalian auditory system do not regenerate, and their loss leads to irreversible hearing loss. Aminoglycosides induce auditory hair cell death in vitro, and evidence suggests that phosphatidylinositol-3-kinase/Akt signaling opposes gentamicin toxicity via its downstream target, the protein kinase Akt. We previously demonstrated that somatostatin-a peptide with hormone/neurotransmitter properties-can protect hair cells from gentamicin-induced hair cell death in vitro, and that somatostatin receptors are expressed in the mammalian inner ear. However, it remains unknown how this protective effect is mediated. In the present study, we show a highly significant protective effect of octreotide (a drug that mimics and is more potent than somatostatin) on gentamicin-induced hair cell death, and increased Akt phosphorylation in octreotide-treated organ of Corti explants in vitro. Moreover, we demonstrate that somatostatin receptor-1 knockout mice overexpress somatostatin receptor-2 in the organ of Corti, and are less susceptible to gentamicin-induced hair cell loss than wild-type or somatostatin-1/somatostatin-2 double-knockout mice. Finally, we show that octreotide affects auditory hair cells, enhances spiral ganglion neurite number, and decreases spiral ganglion neurite length.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Inner Ear Research (Bodmer)
UniBasel Contributors:Bodmer, Daniel K
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Public Library of Science
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:17 Jul 2020 09:04
Deposited On:17 Jul 2020 09:04

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