Cerebellar granule cells as a model to study mechanisms of neuronal apoptosis or survival in vivo and in vitro.
Cerebellar granule cells as a model to study mechanisms of neuronal apoptosis or survival in vivo and in vitro.
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DOI：
10.1080/147342202753203087
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发表时间：
2002-01-01
期刊：
影响因子：
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通讯作者：
Contestabile, Antonio
中科院分区：
文献类型：
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作者：
Contestabile, Antonio
小脑的颗粒细胞构成哺乳动物脑中最大的同质神经元群体。由于其出生后的一代和可行性的良好表征的原代在体外培养，小脑颗粒细胞是一个模型的选择的细胞和分子相关的生存/凋亡和神经变性/神经保护机制的研究。本综述主要涉及的机制和因素，促进小脑颗粒神经元的生存或凋亡消除的最新数据，特别关注在基因表达和细胞信号通路的诱导水平的分子相关性。首先分析了体内发育，特别是几种神经营养因子和谷氨酸受体的NMDA亚型所起的作用。然后，在原代体外培养模型中研究了存活/凋亡的机制，其中神经营养因子作用于小脑颗粒细胞的作用随后是来自钾/血清戒断范例的大量数据。Bcl家族的一些关键基因，一些激酶系统和转录因子的作用主要突出。此外，线粒体，自由基和caspase家族的蛋白酶的参与被认为是。最后，使用小脑颗粒神经元在原代培养，以实验解决神经退行性变和药理学神经保护的问题被认为是，在坏死和凋亡之间的边界模型，如兴奋性毒性神经元损伤的一些意见。颗粒神经元中由明显不相关的刺激（如神经营养因子和神经递质/神经调质）激活的细胞信号通路的重叠被强调以揭示神经元中由活动所发挥的特殊“营养”作用。最后，强调了在体内和体外发育过程中设计和执行小脑颗粒神经元概念上等同的实验的优势。在回顾材料的基础上，它的结论是，小脑颗粒神经元已获得了一个特殊的位置，在现代神经科学作为一个最可靠的模型，用于研究神经发育，功能和病理。
Granule cells of the cerebellum constitute the largest homogeneous neuronal population of mammalian brain. Due to their postnatal generation and the feasibility of well characterized primary in vitro cultures, cerebellar granule cells are a model of election for the study of cellular and molecular correlates of mechanisms of survival/apoptosis and neurodegeneration/neuroprotection. The present review mainly deals with recent data on mechanisms and factors promoting survival or apoptotic elimination of cerebellar granule neurons, with a particular focus on the molecular correlates at the level of gene expression and induction of cellular signal pathways. The in vivo development is first analysed with particular reference to the role played by several neurotrophic factors and by the NMDA subtype of glutamate receptor. Then, mechanisms of survival/apoptosis are examined in the model of primary in vitro cultures, where the role of neurotrophins acting on cerebellar granule cells is followed by the large deal of data coming from the paradigm of potassium/serum withdrawal. The role of some key genes of the Bcl family, of some kinase systems and of transcriptional factors is primarily highlighted. Furthermore, the involvement of mitochondria, free radicals and proteases of the caspase family is considered. Finally, the use of cerebellar granule neurons in primary culture to experimentally address the issue of neurodegeneration and pharmacological neuroprotection is considered, with some comments on models at the borderline between necrosis and apoptosis, such as the excitotoxic neuronal damage. The overlapping of cellular signal pathways activated in granule neurons by apparently unrelated stimuli, such as neurotrophins and neurotransmitters/neuromodulators is stressed to put into light the special 'trophic' role played by activity in neurons. Finally, the advantage of designing and performing conceptually equivalent experiments on cerebellar granule neurons during development in vivo and in vitro, is stressed. On the basis of the reviewed material, it is concluded that cerebellar granule neurons have acquired a special position in modern neuroscience as one of the most reliable models for the study of neural development, function and pathology.