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谷氨酸-天冬氨酸转运体(GLAST)在人耳蜗中的表达及其在各种患者群体中的分布。

The expression of glutamate aspartate transporter (GLAST) within the human cochlea and its distribution in various patient populations.

机构信息

Department of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1624, USA.

出版信息

Brain Res. 2013 Sep 5;1529:134-42. doi: 10.1016/j.brainres.2013.06.040. Epub 2013 Jul 11.

Abstract

Glutamate plays an important role in the central nervous system as an excitatory neurotransmitter. However, its abundance can lead to excitotoxicity which necessitates the proper function of active glutamate transporters. The glutamate-aspartate transporter (GLAST) has been shown to exist and function within non-human cochlear specimens regulating the inner ear glutamate concentration. In this study, we examined human cochleas from formalin-fixed celloidin-embedded temporal bone specimens of three different types of patients (Meniere's disease, normal controls, and other otopathologic conditions) and examined the differential expression of GLAST in the spiral ligament of the basal, middle, and apical turns of the cochlea. Immunohistochemical staining was performed with polyclonal antibodies against GLAST and image analysis was carried out with the Image J analysis software. In contrast to other studies with non-human specimens, GLAST was expressed in the spiral ligament fibrocytes but was not detected in the satellite cells of the spiral ganglia or supporting cells of the Organ of Corti in the human cochlea. Our data also showed that GLAST expression significantly differs in the basal and apical turns of the cochlea. Lastly, post-hoc analysis showed a difference in the GLAST immunoreactive area of patients with Meniere's disease when compared to that of patients with other otopathologic conditions-such as presbycusis or ototoxicity. These results may potentially lead to further understanding of different disease states that affect hearing.

摘要

谷氨酸作为一种兴奋性神经递质,在中枢神经系统中起着重要作用。然而,其含量过多会导致兴奋性毒性,这就需要活性谷氨酸转运体的正常功能。已证实谷氨酸-天冬氨酸转运体(GLAST)存在于非人类耳蜗标本中,并发挥作用,调节内耳谷氨酸浓度。在这项研究中,我们检查了来自三种不同类型患者(梅尼埃病、正常对照组和其他耳病理状况)的福尔马林固定细胞素包埋颞骨标本的人耳蜗,并检查了 GLAST 在耳蜗基底、中和顶部螺旋韧带中的差异表达。使用针对 GLAST 的多克隆抗体进行免疫组织化学染色,并使用 Image J 分析软件进行图像分析。与其他使用非人类标本的研究不同,GLAST 在螺旋韧带成纤维细胞中表达,但在螺旋神经节的卫星细胞或 Corti 器的支持细胞中未检测到。我们的数据还表明,GLAST 在耳蜗的基底和顶部表达差异显著。最后,事后分析显示,与其他耳病理状况(如老年性聋或耳毒性)患者相比,梅尼埃病患者的 GLAST 免疫反应面积存在差异。这些结果可能有助于进一步了解影响听力的不同疾病状态。

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