Somatostatin and gentamicin‐induced auditory hair cell loss

Caelers, Antje; Monge, Arianne; Brand, Yves; Bodmer, Daniel

doi:10.1002/lary.20058

Cited by 11 publications

(16 citation statements)

References 22 publications

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“…However, we have recently demonstrated that somatostatin can protect HCs from aminoglycoside toxicity in a dose-dependent manner in vitro [19]. It is reasonable to assume that this neuroprotective effect of somatostatin on HCs was mediated by SST1 or SST2 receptors; however, this has not yet been experimentally proven.…”

Section: Discussionmentioning

confidence: 99%

“…In an additional study, somatostatin-producing cells were observed in the covering epithelium of the spiral prominence and in the epithelium of the intermediate and rugosal part of the endolymphatic sac [17,18]. In a recent publication from our group, we demonstrated expression of SST1 and SST2 mRNA in the postnatal rat cochlea and we reported on a dose-dependent protective effect of somatostatin on gentamicin-induced HC loss in vitro [19]. …”

Section: Introductionmentioning

confidence: 99%

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The somatostatinergic system in the mammalian cochlea

et al. 2011

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BackgroundLittle is known about expression and function of the somatostatinergic system in the mammalian cochlea. We have previously shown that somatostatin administration may have a protective effect on gentamicin-induced hair cell loss. In this study, we have analyzed the cochlear expression of somatostatin receptor 1 (SST1) and somatostatin receptor 2 (SST2) at both the mRNA and the protein level in wild-type mice, as well as in SST1 and SST2 knock-out (KO) mice and in cultivated neurosensory cells.ResultsWe demonstrate that the somatostatin receptors SST1 and SST2 are specifically expressed in outer and inner hair cells (HCs) of the organ of Corti (OC), as well as in defined supporting cells. The expression of SST1 and SST2 receptors in cultivated P5 mouse OC explants was similar to their expression in inner and outer hair cells. Somatostatin itself was not expressed in the mammalian cochlea, suggesting that somatostatin reaches its receptors either through the blood-labyrinthine barrier from the systemic circulation or via the endolymphatic duct from the endolymphatic sac. We used mice with a deletion of either SST1 or SST2 to learn more about the regulation of SST1 and SST2 receptor expression. We demonstrate that in SST1 KO mice, SST2 was expressed in outer HCs and Deiters' cells, but not in pillar cells or inner HCs, as compared with wild-type mice. In contrast, in SST2 KO mice, the expression pattern of the SST1 receptor was not altered relative to wild-type mice.ConclusionsThese findings reveal that somatostatin receptors demonstrate specific expression in HCs and supporting cells of the mouse cochlea, and that absence of SST1 alters the expression of SST2. This specific expression pattern suggests that somatostatin receptors may have important functional roles in the inner ear.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The somatostatinergic system in the mammalian cochlea

et al. 2011

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“…Both drugs damage mainly HCs, resulting in apoptotic HCs death [55,56]. Our group has demonstrated that SST can protect against aminoglycoside toxicity in a dosage-dependent manner in vitro [57]. Therefore, we hypothesized that the somatostatinergic system within the cochlea may have neuroprotective properties.…”

Section: Discussionmentioning

confidence: 99%

Somatostatin Receptor Types 1 and 2 in the Developing Mammalian Cochlea

Bodmer

Brand²,

Radojević³

2012

Dev Neurosci

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The neuropeptide somatostatin (SST) exerts several important physiological actions in the adult central nervous system through interactions with membrane-bound receptors. Transient expression of SST and its receptors has been described in several brain areas during early ontogeny. It is therefore believed that SST may play a role in neural maturation. The present study provides the first evidence for the developmental expression of SST receptors in the mammalian cochlea, emphasizing their possible roles in cochlear maturation. In the developing mouse cochlea, cells immunoreactive to somatostatin receptor 1 (SSTR1) and somatostatin receptor 2 (SSTR2) were located in the embryonic cochlear duct on Kolliker’s organ as early as embryonic day (E) 14 (E14). At E17, the expression of both receptors was high and already located at the hair cells and supporting cells along the length of the cochlear duct, which have become arranged into the characteristic pattern for the organ of Corti (OC) at this stage. At birth, SSTR1- and SSTR2-containing cells were only localized in the OC. In general, immunoreactivity for both receptors increased in the mouse cochlea from postnatal day (P) 0 (P0) to P10; the majority of immunostained cells were inner hair cells, outer hair cells, and supporting cells. Finally, a peak in the mRNA and protein expression of both receptors is present near the time when they respond to physiological hearing (i.e., hearing of airborne sound) at P14. At P21, SSTR1 and SSTR2 levels decrease dramatically. A similar developmental pattern was observed for SSTR1 and SSTR2 mRNA, suggesting that the expression of the SSTR1 and SSTR2 genes is controlled at the transcriptional level throughout development. In addition, we observed reduced levels of phospho-Akt and total Akt in SSTR1 knockout and SSTR1/SSTR2 double-knockout mice compared with wild-type mice. We know from previous studies that Akt is involved in hair cell survival. Taken together, the dynamic nature of SSTR1 and SSTR2 expression at a time of major developmental changes in the cochlea suggests that SSTR1 and SSTR2 (and possibly other members of this family) are involved in the maturation of the mammalian cochlea.

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“…They were maintained for 48 h in culture medium for recovery. OCs were then exposed to gentamicin at the concentration of 0.5 m M for 2, 4, 6, 9, and 15 h. We recently demonstrated that this concentration of gentamicin results in significant HC loss after 15 h [Caelers et al, 2009]. Control explants were maintained in culture medium alone for 0 and 15 h. For each time point, 1 OC was studied.…”

Section: Gentamicin Time Course Experimentsmentioning

confidence: 99%

Stress and Survival Pathways in the Mammalian Cochlea

Caelers¹,

Radojević²,

Traenkle

et al. 2010

Audiol Neurotol

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Studies conducted over the last few years demonstrated that signaling pathways that operate in the organs of Corti (OC) play a central role in survival and death of hair cells. An important goal of molecular otology is to characterize these signaling pathways in normal inner ears and inner ears exposed to a variety of different forms of stress, such as ototoxic substances and noise overexposure. In this study, we used high-performance reverse protein microarray technology and phospho-specific antibodies to examine the activation status of defined molecules involved in cellular signaling. We demonstrate that reverse protein microarrays based on the highly sensitive planar-waveguide technology provide an effective and high-throughput means to assess the activation state of key molecules involved in apoptotic and prosurvival signaling in microdissected OC explants over time. In this study, we show that gentamicin and a specific NF-ĸB inhibitor increase the ratio of phospho-c-Jun/c-Jun in OC explants of postnatal rats soon after exposure to these drugs. In addition, we found a decrease in the phospho-Akt/Akt ratio in OC explants early after NF-ĸB inhibition. Finally, we observed an early and consistent decrease in the phospho-p38/p38 ratio in OC explants exposed to the NF-ĸB inhibitor and only a transient decrease in this ratio in OC examples after gentamicin exposure.

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Somatostatin and gentamicin‐induced auditory hair cell loss

Abstract: Decreased hair cell loss in somatostatin-treated samples that had been exposed to gentamicin provides evidence for a protective effect of somatostatin in aminoglycoside-induced hair cell death in vitro.

Cited by 11 publications

References 22 publications

The somatostatinergic system in the mammalian cochlea

The somatostatinergic system in the mammalian cochlea

Somatostatin Receptor Types 1 and 2 in the Developing Mammalian Cochlea

Stress and Survival Pathways in the Mammalian Cochlea

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