Hartlage-Rübsamen M, Rubel E W
Virginia Merrill Bloedel Hearing Research Center, Department of Otolaryngology, Head and Neck Surgery, University of Washington, Seattle 98195, USA.
J Comp Neurol. 1996 Jul 29;371(3):448-60. doi: 10.1002/(SICI)1096-9861(19960729)371:3<448::AID-CNE7>3.0.CO;2-2.
Following cochlea removal in developing chicks, about 30% of the neurons in the ipsilateral second-order auditory nucleus, nucleus magnocellularis, undergo cell death. Administration of chloramphenicol, a mitochondrial protein synthesis inhibitor, results in a pronounced increase in deafferentation-induced cell death. In this study, we examined whether the chloramphenicol enhancement of deafferentation-induced cell death reveals the same ultrastructural characteristics that are seen in degenerating nucleus magnocellularis neurons after cochlea removal alone. Unilateral cochlea removal was performed on anaesthetized posthatch chicks. One group of animals was simultaneously treated with chloramphenicol. Six, twelve, or twenty-four hours following cochlea removal, n. magnocellularis neurons were studied by routine transmission electron microscopy. Particular attention was paid to the integrity of the polyribosomes and rough endoplasmic reticulum. Two ultrastructurally different types of neuronal degeneration were observed in the deafferented nucleus magnocellularis neurons: an early onset electron-lucent type that always involved ribosomal dissociation and a late-onset electron-dense type displaying nuclear pyknosis and severely damaged mitochondria. The percentage of nucleus magnocellularis neurons displaying ribosomal disintegration following cochlea removal was found to be markedly increased after chloramphenicol treatment. This finding suggests that mitochondrial function is important for the maintenance of a functional protein synthesis apparatus following deafferentation.
在发育中的雏鸡去除耳蜗后，同侧二级听觉核（巨细胞核）中约30%的神经元会发生细胞死亡。给予线粒体蛋白质合成抑制剂氯霉素会导致去传入诱导的细胞死亡显著增加。在本研究中，我们研究了氯霉素增强去传入诱导的细胞死亡是否揭示了与单独去除耳蜗后退化的巨细胞核神经元相同的超微结构特征。对麻醉后的雏鸡进行单侧耳蜗切除术。一组动物同时接受氯霉素治疗。在去除耳蜗后的6、12或24小时，通过常规透射电子显微镜研究巨细胞核神经元。特别关注多核糖体和粗面内质网的完整性。在去传入的巨细胞核神经元中观察到两种超微结构不同类型的神经元退化：一种是早期出现的电子透明型，总是涉及核糖体解离；另一种是晚期出现的电子致密型，表现为核固缩和严重受损的线粒体。发现氯霉素治疗后，去除耳蜗后显示核糖体解体的巨细胞核神经元百分比显著增加。这一发现表明，线粒体功能对于去传入后维持功能性蛋白质合成装置很重要。
