Bcl2 enhances survival of newborn neurons in the normal and ischemic hippocampus
Bcl2 enhances survival of newborn neurons in the normal and ischemic hippocampus
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DOI：
10.1002/jnr.21036
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发表时间：
2006-11-01
影响因子：
4.2
通讯作者：
Hori, Masatsugu
中科院分区：
文献类型：
--
作者：
Sasaki, Tsutomu;Kitagawa, Kazuo;Hori, Masatsugu
成年海马区的神经前体细胞不断增殖并分化为神经元谱系，缺血损伤可促进海马神经发生。然而，在最初的几周内，新生神经元的数量呈进行性减少，因此，提高新生神经元的存活率似乎是治疗策略的关键。BCL-2是中枢神经系统发育过程中程序性细胞死亡以及细胞凋亡和坏死性死亡的重要调节因子。因此，我们测试了在正常和缺血条件下，Bcl-2过表达是否提高了成年小鼠海马区新生神经元的存活率。海马齿状回中的许多新生神经元发生了凋亡。在NSE-bcl2转基因小鼠中，人Bcl2的表达始于未成熟神经元阶段，并在存活的成熟神经元中保持恒定。BCL-2显著增加了两种情况下新生神经元的存活率，尤其是在缺血后，NSE-BCL-2转基因小鼠新生神经元的细胞死亡减少。我们还用BrdU标记的方法阐明了在原代培养的海马神经元中，Bcl2过表达对提高新生神经元存活率的作用。这些结果表明，在正常和缺血条件下，Bcl2在成年海马神经发生中起关键作用。(C)2006年Wiley-Liss，Inc.
Neuronal progenitors in the adult hippocampus continually proliferate and differentiate to the neuronal lineage, and ischemic insult promotes hippocampal neurogenesis. However, newborn neurons show a progressive reduction in numbers during the initial few weeks, therefore, enhanced survival of newborn neurons seems to be essential for therapeutic strategy. Bcl-2 is a crucial regulator of programmed cell death in CNS development and in apoptotic and necrotic cell death. Therefore, we tested whether Bcl-2 overexpression enhances survival of newborn neurons in the adult mouse hippocampus under normal and ischemic conditions. Many newborn neurons in the hippocampal dentate gyrus undergo apoptosis. Human Bcl-2 expression in NSE-bcl-2 transgenic mice began at the immature neuronal stage and remained constant in surviving mature neurons. Bcl-2 significantly increased survival of newborn neurons under both conditions, but particularly after ischemia, with decreased cell death of newborn neurons in NSE-bcl-2 transgenic mice. We also clarified the effect by Bcl-2 overexpression of enhanced survival of newborn neurons in primary hippocampal cultures with BrdU labeling. These findings suggest that Bcl-2 plays a crucial role in adult hippocampal neurogenesis under normal and ischemic conditions. (c) 2006 Wiley-Liss, Inc.