Department of Biomedicine and Clinic for Otorhinolaryngology, University Hospital Basel, Basel, Switzerland.
Dev Neurosci. 2012;34(4):342-53. doi: 10.1159/000341291. Epub 2012 Sep 13.
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.
神经肽生长抑素 (SST) 通过与膜结合受体相互作用，在成人中枢神经系统中发挥多种重要的生理作用。在早期胚胎发生过程中，已经在几个脑区描述了 SST 和其受体的短暂表达。因此，人们认为 SST 可能在神经成熟中发挥作用。本研究首次提供了 SST 受体在哺乳动物耳蜗中发育表达的证据，强调了它们在耳蜗成熟中的可能作用。在发育中的小鼠耳蜗中，SSTR1 和 SSTR2 受体的免疫反应性细胞早在胚胎第 14 天 (E14) 就在耳蜗管的科尔蒂器上定位。在 E17 时，两种受体的表达均较高，并且已经位于耳蜗管的毛细胞和支持细胞上，此时耳蜗管已经排列成具有特征性的柯蒂器 (OC) 模式。在出生时，含有 SSTR1 和 SSTR2 的细胞仅位于 OC 中。一般来说，从出生后第 0 天 (P0) 到第 10 天，两种受体在小鼠耳蜗中的免疫反应性增加；大多数免疫染色细胞为内毛细胞、外毛细胞和支持细胞。最后，两种受体的 mRNA 和蛋白表达均在其对生理听力 (即空气传播声音的听力) 作出反应的时间附近达到峰值，即 P14 时。在 P21 时，SSTR1 和 SSTR2 水平急剧下降。SSTR1 和 SSTR2 mRNA 也观察到类似的发育模式，这表明 SSTR1 和 SSTR2 基因的表达在整个发育过程中均受转录水平的控制。此外，我们还观察到 SSTR1 敲除和 SSTR1/SSTR2 双敲除小鼠中磷酸化 Akt 和总 Akt 的水平低于野生型小鼠。我们从之前的研究中知道，Akt 参与毛细胞的存活。综上所述，在耳蜗发生重大发育变化的时期，SSTR1 和 SSTR2 表达的动态性质表明 SSTR1 和 SSTR2(可能还有该家族的其他成员)参与了哺乳动物耳蜗的成熟。
