Developmental cell death in dopaminergic neurons of the substantia nigra of mice
Developmental cell death in dopaminergic neurons of the substantia nigra of mice
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DOI：
10.1002/1096-9861(20000828)424:3
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发表时间：
2000-08-28
影响因子：
2.5
通讯作者：
Przedborski, S
中科院分区：
文献类型：
--
作者：
Jackson-Lewis, V;Vila, M;Przedborski, S
大鼠黑质致密部 (SNpc) 中的多巴胺能神经元在发育过程中经历自然细胞死亡。关于发育中小鼠的 SNpe 多巴胺能神经元中是否发生这种现象存在争议。在此，通过使用一系列形态学技术，我们表明许多 SNpc 神经元满足细胞凋亡的标准，并且 SNpe 中凋亡神经元的数量从出生后第 2 天到第 32 天以时间依赖性方式变化。这些垂死的神经元还显示出 DNA 碎片、激活的 caspase-3 和 p-肌动蛋白裂解的证据。一些（但不是全部）SNpc 凋亡神经元仍然表达其表型标记酪氨酸羟化酶，证实了其多巴胺能性质。与靶点来源的营养支持在调节发育细胞死亡中的重要性一致，我们证明通过局部注射喹啉酸（QA）破坏内在纹状体神经元可显着增强 SNpc 细胞凋亡的程度，并导致成年 SNpe 多巴胺能神经元数量减少。为了加强观察到的 SNpc 发育细胞死亡的凋亡性质，我们证明抗凋亡蛋白 Bcl-2 的过度表达可减弱自然和 QA 诱导的 SNpc 细胞凋亡。本研究提供了令人信服的证据，表明小鼠 SNpc 中确实发生了具有细胞凋亡形态的发育性神经元死亡，并且该过程在调节 SNpc 中多巴胺能神经元的成年数量中发挥着关键作用。 (C) 2000 Wiley-Liss, Inc.
Dopaminergic neurons in the substantia nigra pars compacta (SNpc) undergo natural cell death during development in rats. Controversy exists as to the occurrence of this phenomenon in SNpe dopaminergic neurons in the developing mouse. Herein, by using an array of morphologic techniques, we show that many SNpc neurons fulfill the criteria for apoptosis and that the number of apoptotic neurons in the SNpe vary in a time-dependent manner from postnatal day 2 to 32. These dying neurons also show evidence of DNA fragmentation, of activated caspase-3, and of cleavage of p-actin. Some, but not all of the SNpc apoptotic neurons still express their phenotypic marker tyrosine hydroxylase, confirming their dopaminergic nature. Consistent with the importance of target-derived trophic support in modulating developmental cell death, we demonstrate that destruction of intrinsic striatal neurons by a local injection of quinolinic acid (QA) dramatically enhances the magnitude of SNpc apoptosis and results in a lower number of adult SNpe dopaminergic neurons. Strengthening the apoptotic nature of the observed SNpc developmental cell death, we demonstrate that overexpression of the anti-apoptotic protein Bcl-2 attenuates both natural and QA-induced SNpc apoptosis. The present study provides compelling evidence that developmental neuronal death with a morphology of apoptosis does occur in the SNpc of mice and that this process plays a critical role in regulating the adult number of dopaminergic neurons in the SNpc. (C) 2000 Wiley-Liss, Inc.