Garden G A, Redeker-DeWulf V, Rubel E W
Virginia Merrill Bloedel Hearing Research Center, Department of Physiology and Biophysics, University of Washington, Seattle 98195, USA.
J Comp Neurol. 1995 Aug 28;359(3):412-23. doi: 10.1002/cne.903590305.
Neuronal survival in the cochlear nucleus of young animals is regulated by afferent activity. Removal or blockade of nerve VIII input results in the death of 20-40% of neurons in the cochlear nucleus, nucleus magnocellularis (NM), of the 10-14 days posthatch chick. Neuronal death in NM is preceded by complete failure of protein synthesis and degradation of ribosomes. In addition, there is a biphasic change in the immunoreactivity of ribosomes for a monoclonal antiribosomal RNA antibody, Y10B. Initially, the entire population of afferent-deprived NM neurons loses Y10B immunoreactivity, but, after 6 or 12 hours of afferent deprivation, lack of Y10B immunoreactivity specifically marks dying NM neurons. Whether RNA synthesis is also altered in afferent-deprived NM neurons has not previously been studied. To determine whether RNA synthesis in NM neurons is regulated by loss of afferent activity, we injected chicks with 3H-uridine following unilateral cochlea removal and measured the incorporation of RNA precursor with tissue autoradiography. As early as 1 hour after cochlea removal, there was a significant decrease in 3H-uridine incorporation by afferent-deprived NM neurons. After longer periods of afferent deprivation (6 or 12 hours), the majority of dying NM neurons (marked by loss of Y10B immunoreactivity) fail to incorporate RNA precursor. Six or 12 hours following cochlea removal, the subpopulation of surviving NM neurons incorporates 3H-uridine at increased levels over those observed 1 or 3 hours after cochlea removal. These findings suggest that nuclear function is regulated by afferent synaptic activity and that failure of RNA synthesis occurs early in the cell death process.
幼龄动物耳蜗核中的神经元存活受传入活动调控。切除或阻断第八对脑神经输入会导致孵化后10 - 14天雏鸡的耳蜗核大细胞神经核（NM）中20% - 40%的神经元死亡。NM中的神经元死亡之前会出现蛋白质合成完全失败以及核糖体降解的情况。此外，针对单克隆抗核糖体RNA抗体Y10B，核糖体的免疫反应性存在双相变化。最初，所有传入剥夺的NM神经元群体都会失去Y10B免疫反应性，但在传入剥夺6或12小时后，缺乏Y10B免疫反应性会特异性地标记即将死亡的NM神经元。此前尚未研究传入剥夺的NM神经元中RNA合成是否也会改变。为了确定NM神经元中的RNA合成是否受传入活动丧失的调控，我们在单侧耳蜗切除后给雏鸡注射3H - 尿苷，并通过组织放射自显影测量RNA前体的掺入情况。早在耳蜗切除后1小时，传入剥夺的NM神经元对3H - 尿苷的掺入就显著减少。在更长时间的传入剥夺（6或12小时）后，大多数即将死亡的NM神经元（以失去Y10B免疫反应性为标记）无法掺入RNA前体。耳蜗切除6或12小时后，存活的NM神经元亚群对3H - 尿苷的掺入水平高于耳蜗切除后1或3小时观察到的水平。这些发现表明核功能受传入突触活动调控，且RNA合成失败在细胞死亡过程早期就已发生。
