The somatostatinergic system in the mammalian cochlea

Radojević, Vesna; Hanusek, Claudia; Setz, Cristian; Brand, Yves; Kapfhammer, Josef P.; Bodmer, Daniel

doi:10.1186/1471-2202-12-89

Cited by 8 publications

(17 citation statements)

References 30 publications

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“…In addition, it is noteworthy that the developmental pattern of SSTR1 and SSTR2 expression are similar. In our previous publication we observed that deletion of one receptor subtype was compensated by an overexpression of the other receptor subtype [25]. These findings support the idea that both receptors have a related function in the inner ear.…”

Section: Discussionsupporting

confidence: 76%

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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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Section: Discussionsupporting

confidence: 76%

“…Our previous study demonstrated that SSTR1 and SSTR2 mRNA and protein were expressed in the adult mouse cochlea, and were localized in the IHC, outer hair cells (OHC), and supporting cells of the OC [25]. SSTR3, 4, and 5 have not been shown to be essential for the function of SST [10].…”

Section: Introductionmentioning

confidence: 99%

Somatostatin Receptor Types 1 and 2 in the Developing Mammalian Cochlea

Bodmer

Brand²,

Radojević³

2012

Dev Neurosci

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“…SSTR2 protein was strongly expressed in DeC, and to a lesser extent in OHC, but was absent from PiC and IHC compared with WT mice. In SSTR2 KO the staining pattern did not differ from that of WT mice [30]. In addition, no major compensatory regulation of SST or individual SSTRs has been described as a consequence of the genetic deletion of SSTR1 or SSTR2 in specific brain regions [37].…”

Section: Expression Of Somatostatin Receptors In Cochlea Of Knock Outmentioning

confidence: 88%

“…In the retina, recently major alterations of SST content were demonstrated as a consequence of SSTR1 or SSTR2 deletion [38]. Indeed, SSTR1 loss causes an increased expression of SSTR2 [30]. In the DKO mouse cochlea the expression of SSTR3 mRNA, as measured with quantitative qPCR in OC explants from P21 day-old mice was not significantly changed but the expression of SSTR4 in OC explants from P21 day-old mice was significantly decreased compared to age matched OC explants from WT mice.…”

Section: Expression Of Somatostatin Receptors In Cochlea Of Knock Outmentioning

confidence: 99%

“…The increase of these proteins until P14 may be necessary for the growth and development of the OC, although not for mature hearing. In addition, it is noteworthy that the developmental pattern Figure 2D) [30]. 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 [30].…”

Section: Somatostatin and Localization Of Somatostatin Receptors In Tmentioning

confidence: 99%

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Targeting the somatostatin receptors as a therapeutic approach for the preservation and protection of the mammalian cochlea from excitotoxicity

Radojević¹,

Brand²,

Levano³

et al. 2013

Translational Neuroscience

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The neuropeptide somatostatin (SST) is an important modulator of neurotransmission in the central nervous system (CNS) and binds to G-protein-coupled receptors (SSTR1-5) on target cells. Little is known about the expression and function of the somatostatinergic system in the mammalian cochlea. We analyzed the expression of SSTR1-SSTR5 in the immature mammalian cochlea. The peak in the expression of SSTR1 and SSTR2 at mRNA and protein level is around the onset of hearing to airborne sound, at postnatal day (P)14. This suggests their involvement in the maturation of the mammalian cochlea. We demonstrated that all five receptors are expressed in the inner hair cells (IHC) and outer hear cells (OHC) as well as in defined supporting cells of the organ of Corti (OC) in the adult mouse cochlea. A similar expression of the SSTRs in the IHC and OHC was found in cultivated P6 mouse OC explants as well as in neuroepithelial cell culture. In order to learn more about the regulation of SSTRs, we used mice with either a deletion of SSTR1, SSTR2 or SSTR1/SSTR2 double knock out (DKO). In DKO mice, SSTR5 was up-regulated and SSTR3 and SSTR4 were down regulated. These findings provide evidence of a compensatory regulation in the mammalian cochlea as a consequence of a receptor subtype deletion. In addition, we observed reduced levels of phospho-Akt and total-Akt in SSTR1 KO and DKO mice as compared to wild type (WT) mice. Akt is likely to be involved in hair cell survival. Most importantly, we found improved hair cell survival in somatostatin and octreotide treated OC explants that had been exposed to gentamicin compared to those explants exposed to gentamicin alone. These findings propose that the somatostatinergic system within the cochlea may have neuroprotective properties.

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Expression and localization of somatostatin receptor types 3, 4 and 5 in the wild-type, SSTR1 and SSTR1/SSTR2 knockout mouse cochlea

Radojević

Bodmer

2014

Cell Tissue Res

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Somatostatin (SST) is a peptide hormone that exerts inhibitory effects mediated through binding to specific cell surface G protein-coupled receptors, of which five distinct subtypes (SSTR1-SSTR5) have been characterized. Our study performed on mouse cochlear hair cells shows the expression and localization of the three receptors (SSTR3-SSTR5) in wild-type (WT), single-knockout (SSTR1 KO) and double-knockout SSTR1/SSTR2 (DKO) mice. Similar SSTRs expression were observed in the inner hair cells (IHC), outer hair cells (OHC) and supporting cells of cultivated P7 mouse organ of Corti (OC) explants as well as in cultivated cochlear neuroepithelial supporting cells (NEsc). We found differences in the expression of SSTR3-5 in WT, SSTR1 KO and DKO mouse cochlea, which might be explained as a compensatory effect in the cochlea after the loss of SSTR1 and/or SSTR2.

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The somatostatinergic system in the mammalian cochlea

Cited by 8 publications

References 30 publications

Somatostatin Receptor Types 1 and 2 in the Developing Mammalian Cochlea

Somatostatin Receptor Types 1 and 2 in the Developing Mammalian Cochlea

Targeting the somatostatin receptors as a therapeutic approach for the preservation and protection of the mammalian cochlea from excitotoxicity

Expression and localization of somatostatin receptor types 3, 4 and 5 in the wild-type, SSTR1 and SSTR1/SSTR2 knockout mouse cochlea

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