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传入对鸡脑干听觉核的影响:氨基酸掺入的停止作为年龄依赖性跨神经元变性的前奏。

Afferent influences on brain stem auditory nuclei of the chicken: cessation of amino acid incorporation as an antecedent to age-dependent transneuronal degeneration.

作者信息

Steward O, Rubel E W

出版信息

J Comp Neurol. 1985 Jan 15;231(3):385-95. doi: 10.1002/cne.902310308.

Abstract

Previous studies of the avian auditory system have revealed that removal of the peripheral receptor (the cochlea) leads to a transneuronal degeneration of auditory relay neurons in nucleus magnocellularis (NM) of the brain stem. An early manifestation of the degeneration which can be observed within 12 hours is a decrease of histochemical staining for RNA (Nissl staining); such a decrease could reflect an alteration in protein synthetic activity within the NM neurons. The present study evaluates this possibility by determining whether the cochlea removal led to an alteration incorporation of protein precursors in the target neurons which exhibit transneuronal degeneration and if so, how early the changes appeared. The cochlea was removed unilaterally in seventeen 10-day-old chicks and two 66-week-old mature chickens, and incorporation of protein precursors was evaluated in the neurons of NM at 0.5, 1.5, 3, 6, 12, and 24 hours following the cochlea removal. Each chick received an intravenous injection of 3H leucine, and was allowed to survive for 30 minutes after the injection of precursor. The brains were then prepared for autoradiography. The extent of incorporation by neurons in NM was determined by counting grains overlying each cell body and determining grain density/micrometers2 of neuron cross-sectional area. We found that auditory relay neurons whose synaptic inputs have been silenced exhibit dramatic decreases in protein synthesis within 30 minutes after removal of the cochlea; leucine incorporation was reduced by about 50%. In chicks sacrificed 3 to 24 hours after removal of the cochlea, some neurons (about 1/3) were entirely unlabeled despite heavy labeling of their neighbors and heavy labeling of all NM neurons on the opposite side of the brain. The remaining neurons exhibited about a 15% reduction in incorporation in comparison with the cells in the contralateral (control) NM. While the decreases in incorporation were apparent at all survival intervals, there was no consistent decrease in Nissl staining until 6 hours after cochlea removal. There were no changes in protein precursor incorporation following removal of the cochlea in adult birds, a result which is in keeping with the relative absence of transneuronal degeneration following removal of the cochlea at maturity. The results suggest a very rapid transneuronal regulation of protein metabolism within target neurons in young animals, perhaps by activity-related events.

摘要

以往对鸟类听觉系统的研究表明,去除外周感受器(耳蜗)会导致脑干大细胞神经核(NM)中的听觉中继神经元发生跨神经元变性。这种变性的早期表现可在12小时内观察到,即RNA组织化学染色(尼氏染色)减少;这种减少可能反映了NM神经元内蛋白质合成活性的改变。本研究通过确定去除耳蜗是否导致表现出跨神经元变性的靶神经元中蛋白质前体掺入的改变,以及如果是这样,变化出现得有多早,来评估这种可能性。在17只10日龄雏鸡和2只66周龄成年鸡中单侧去除耳蜗,并在去除耳蜗后的0.5、1.5、3、6、12和24小时评估NM神经元中蛋白质前体的掺入情况。每只雏鸡静脉注射3H亮氨酸,并在注射前体后存活30分钟。然后将大脑制备用于放射自显影。通过计数每个细胞体上的银粒并确定神经元横截面积的银粒密度/平方微米来确定NM中神经元的掺入程度。我们发现,其突触输入已被沉默的听觉中继神经元在去除耳蜗后30分钟内蛋白质合成显著减少;亮氨酸掺入减少了约50%。在去除耳蜗后3至24小时处死的雏鸡中,一些神经元(约1/3)尽管其相邻神经元和大脑另一侧所有NM神经元都有大量标记,但却完全没有标记。与对侧(对照)NM中的细胞相比,其余神经元的掺入减少了约15%。虽然在所有存活时间间隔内掺入的减少都很明显,但直到去除耳蜗后6小时尼氏染色才出现一致的减少。成年鸟类去除耳蜗后蛋白质前体掺入没有变化,这一结果与成熟时去除耳蜗后相对缺乏跨神经元变性一致。结果表明,幼小动物靶神经元内蛋白质代谢存在非常快速的跨神经元调节,可能是由与活动相关的事件引起的。

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