Multipotent neural precursors can differentiate toward replacement of neurons undergoing targeted apoptotic degeneration in adult mouse neocortex.
Multipotent neural precursors can differentiate toward replacement of neurons undergoing targeted apoptotic degeneration in adult mouse neocortex.
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DOI：
10.1073/pnas.94.21.11663
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发表时间：
1997-10
影响因子：
11.1
通讯作者：
E. Snyder;Cliff Yoon;J. Flax;J. D. Macklis
中科院分区：
文献类型：
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作者：
E. Snyder;Cliff Yoon;J. Flax;J. D. Macklis
经历靶向光解细胞死亡的神经元因细胞凋亡而退化。将克隆性多能神经前体细胞移植到成年小鼠新皮质区域，通过靶向光解作用使 II/III 层锥体神经元发生选择性变性。这些前体细胞整合到选择性神经元死亡区域； 15 +/- 7% 分化为具有退化锥体神经元的许多特征的神经元。它们延伸轴突和树突并建立传入突触接触。在完整的和红藻氨酸损伤的对照成年新皮质中，移植的前体完全分化成神经胶质细胞。这些结果表明，成人新皮质中这种同步凋亡神经元变性产生的微环境改变诱导多能神经前体经历神经元分化，这通常仅在胚胎皮质发生期间发生。研究这种定义的微环境扰动对克隆神经前体分化的影响可能有助于识别正常发育过程中参与承诺和分化的因素。由于光解变性模拟了细胞凋亡性神经退行性疾病的一些机制，这些结果也表明神经前体移植作为新皮质某些疾病的潜在细胞替代或分子支持疗法的可能性，即使在成人中也是如此。
Neurons undergoing targeted photolytic cell death degenerate by apoptosis. Clonal, multipotent neural precursor cells were transplanted into regions of adult mouse neocortex undergoing selective degeneration of layer II/III pyramidal neurons via targeted photolysis. These precursors integrated into the regions of selective neuronal death; 15 +/- 7% differentiated into neurons with many characteristics of the degenerated pyramidal neurons. They extended axons and dendrites and established afferent synaptic contacts. In intact and kainic acid-lesioned control adult neocortex, transplanted precursors differentiated exclusively into glia. These results suggest that the microenvironmental alterations produced by this synchronous apoptotic neuronal degeneration in adult neocortex induced multipotent neural precursors to undergo neuronal differentiation which ordinarily occurs only during embryonic corticogenesis. Studying the effects of this defined microenvironmental perturbation on the differentiation of clonal neural precursors may facilitate identification of factors involved in commitment and differentiation during normal development. Because photolytic degeneration simulates some mechanisms underlying apoptotic neurodegenerative diseases, these results also suggest the possibility of neural precursor transplantation as a potential cell replacement or molecular support therapy for some diseases of neocortex, even in the adult.