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展神经核间神经元在出生后早期发育过程中依赖其靶运动神经元来维持存活。

Abducens internuclear neurons depend on their target motoneurons for survival during early postnatal development.

作者信息

Morcuende Sara, Benítez-Temiño Beatriz, Pecero María Luisa, Pastor Angel M, de la Cruz Rosa R

机构信息

Departamento de Fisiología y Zoología, Facultad de Biología, Universidad de Sevilla, Avda. Reina Mercedes 6, 41012-Sevilla, Spain.

出版信息

Exp Neurol. 2005 Sep;195(1):244-56. doi: 10.1016/j.expneurol.2005.05.003.

Abstract

The highly specific projection of abducens internuclear neurons onto medial rectus motoneurons in the oculomotor nucleus is a good model to evaluate the dependence on target cells for survival during development and in the adult. Thus, the procedure we chose to selectively deprive abducens internuclear neurons of their natural target was the enucleation of postnatal day 1 rats to induce the death of medial rectus motoneurons. Two months later, we evaluated both the extent of reduction in target size, by immunocytochemistry against choline acetyltransferase (ChAT) and Nissl counting, and the percentage of abducens internuclear neurons surviving target loss, by calretinin immunostaining and horseradish peroxidase (HRP) retrograde tracing. Firstly, axotomized oculomotor motoneurons died in a high percentage ( approximately 80%) as visualized 2 months after lesion. In addition, we showed a transient (1 month) and reversible down-regulation of ChAT expression in extraocular motoneurons induced by injury. Secondly, 2 months after enucleation, 61.6% and 60.5% of the population of abducens internuclear neurons appeared stained by retrograde tracing and calretinin immunoreaction, respectively, indicating a significant extent of cell death after target loss (38.4% or 39.5%). By contrast, in the adult rat, neither extraocular motoneurons died in response to axotomy nor abducens internuclear neurons died due to the loss of their target motoneurons induced by the retrograde transport of toxic ricin injected in the medial rectus muscle. These results indicate that, during development, abducens internuclear neurons depend on their target motoneurons for survival, and that they lose this dependence with maturation.

摘要

展神经核间神经元向动眼神经核内的内直肌运动神经元发出高度特异性投射,这是评估发育过程中和成年期神经元存活对靶细胞依赖性的良好模型。因此,我们选择的选择性剥夺展神经核间神经元天然靶标的方法是摘除出生后第1天大鼠的眼球,以诱导内直肌运动神经元死亡。两个月后,我们通过针对胆碱乙酰转移酶(ChAT)的免疫细胞化学和尼氏计数评估靶标大小的减少程度,并通过钙视网膜蛋白免疫染色和辣根过氧化物酶(HRP)逆行追踪评估展神经核间神经元在靶标丧失后存活的百分比。首先,损伤后2个月可见,轴突切断的动眼神经运动神经元有很高比例(约80%)死亡。此外,我们发现损伤诱导眼外肌运动神经元中ChAT表达出现短暂(1个月)且可逆的下调。其次,摘除眼球2个月后,分别有61.6%和60.5%的展神经核间神经元群体通过逆行追踪和钙视网膜蛋白免疫反应染色,表明靶标丧失后细胞死亡程度显著(38.4%或39.5%)。相比之下,在成年大鼠中,眼外肌运动神经元不会因轴突切断而死亡,展神经核间神经元也不会因在内直肌中注射有毒蓖麻毒素逆行运输诱导的靶标运动神经元丧失而死亡。这些结果表明,在发育过程中,展神经核间神经元的存活依赖于其靶标运动神经元,并且随着成熟它们失去了这种依赖性。

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