The cell cycle-apoptosis connection revisited in the adult brain
The cell cycle-apoptosis connection revisited in the adult brain
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DOI：
10.1083/jcb.200505072
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发表时间：
2005-11-21
影响因子：
7.8
通讯作者：
Patterson, PH
中科院分区：
文献类型：
--
作者：
Bauer, S;Patterson, PH
在体内使用胸腺嘧啶类似物如溴脱氧尿苷（BrdU）来标记细胞周期S期的DNA合成，研究了成人神经发生。然而，BrdU也可能标记与细胞增殖不直接相关的DNA合成事件，如DNA修复和/或流产再进入细胞周期，这可能作为有丝分裂后神经元凋亡过程的一部分发生。在本研究中，我们使用了三种表征良好的损伤性神经元凋亡模型，并结合细胞出生（BrdU标记）和死亡（tdt介导的dutp -生物素缺口末端标记）的可视化来研究BrdU在体内成年小鼠脑内掺入的特异性。我们提供的证据表明，BrdU在DNA修复过程中没有明显的掺入，即使将高剂量的BrdU直接注入大脑，也不会在易损或死亡的有丝分裂后神经元中检测到标记。这些发现对围绕成体神经发生的争论具有重要意义：细胞周期再激活与终末分化神经元凋亡之间的联系。
Adult neurogenesis is studied in vivo using thymidine analogues such as bromodeoxyuridine ( BrdU) to label DNA synthesis during the S phase of the cell cycle. However, BrdU may also label DNA synthesis events not directly related to cell proliferation, such as DNA repair and/or abortive reentry into the cell cycle, which can occur as part of an apoptotic process in postmitotic neurons. In this study, we used three well-characterized models of injury-induced neuronal apoptosis and the combined visualization of cell birth (BrdU labeling) and death (Tdt-mediated dUTP-biotin nick end labeling) to investigate the specificity of BrdU incorporation in the adult mouse brain in vivo. We present evidence that BrdU is not significantly incorporated during DNA repair and that labeling is not detected in vulnerable or dying postmitotic neurons, even when a high dose of BrdU is directly infused into the brain. These findings have important implications for a controversy surrounding adult neurogenesis: the connection between cell cycle reactivation and apoptosis of terminally differentiated neurons.