Apoptosis has been recognized to be an essential process during neural development. It is generally assumed that about half of the neurons produced during neurogenesis die before completion of the central nervous system (CNS) maturation, and this process affects nearly all classes of neurons. In this review, we discuss the experimental data in vivo on naturally occurring neuronal death in normal, transgenic and mutant animals, with special attention to the cerebellum as a study model. The emerging picture is that of a dual wave of apoptotic cell death affecting central neurons at different stages of their life. The first wave consists of an early neuronal death of proliferating precursors and young postmitotic neuroblasts, and appears to be closely linked to cell cycle regulation. The second wave affects postmitotic neurons at later stages, and is much better understood in functional terms, mainly on the basis of the neurotrophic concept in its broader definition. The molecular machinery of late apoptotic death of postmitotic neurons more commonly follows the mitochondrial pathway of intracellular signal transduction, but the death receptor pathway may also be involved.Undoubtedly, analysis of naturally occurring neuronal death (NOND) in vivo will offer a basis for parallel and future studies aiming to elucidate the mechanisms of pathologic neuronal loss occurring as the result of conditions such as neurodegenerative disorders, trauma or ischemia.

中文翻译：

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哺乳动物中枢神经系统细胞凋亡的体内细胞和分子机制。

凋亡已被认为是神经发育过程中必不可少的过程。通常认为，在神经发生过程中产生的大约一半神经元在中枢神经系统（CNS）成熟完成之前死亡，并且该过程几乎影响所有类型的神经元。在这篇综述中，我们讨论了正常，转基因和突变动物中自然发生的神经元死亡的体内实验数据，并特别注意小脑作为研究模型。出现的新情况是凋亡细胞死亡的双重波影响了生命中不同阶段的中枢神经元。第一波由增殖的前体和年轻的有丝分裂后成神经细胞的早期神经元死亡组成，并且似乎与细胞周期调控密切相关。第二波在后期影响有丝分裂后神经元，并且在功能上更好地理解，主要是基于神经营养概念的广义定义。核分裂后神经元晚期细胞凋亡死亡的分子机制更普遍地遵循细胞内信号转导的线粒体途径，但也可能涉及死亡受体途径。毫无疑问，体内自然发生的神经元死亡（NOND）的分析将为平行的神经元死亡提供基础。旨在阐明由于神经退行性疾病，外伤或局部缺血等病症而导致的病理性神经元丢失的机制和未来的研究。