Nitric oxide acts in a positive feedback loop with BDNF to regulate neural progenitor cell proliferation and differentiation in the mammalian brain
Nitric oxide acts in a positive feedback loop with BDNF to regulate neural progenitor cell proliferation and differentiation in the mammalian brain
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DOI：
10.1016/s0012-1606(03)00120-9
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发表时间：
2003-06-15
影响因子：
2.7
通讯作者：
Mattson, MP
中科院分区：
文献类型：
--
作者：
Cheng, AW;Wang, SQ;Mattson, MP
一氧化氮（NO）被认为是调节成熟神经元突触可塑性的细胞间信号。我们现在报道一氧化氮也调节小鼠脑神经祖细胞（NPCs）的增殖和分化。用NO合成酶抑制剂L-NAME或NO清道夫血红蛋白处理分离的小鼠皮质神经上皮簇细胞培养物可增加细胞增殖并降低NPC向神经元的分化，而NO供体硝普钠可抑制NPC增殖并增加神经元分化。脑源性神经营养因子（BDNF）降低鼻咽癌细胞增殖，增加分化神经元NO合成酶（nNOS）的表达。BDNF对NPC神经元分化的刺激作用被L-NAME和血红蛋白阻断，提示后者细胞产生的NO抑制相邻NPC的增殖，诱导其神经元分化。数据显示，NO合成酶抑制可增强成年小鼠脑室下区鼻咽癌的增殖并抑制神经元分化，这表明NO在调节成脑神经干细胞从增殖到分化的转变中也起着类似的作用。这些研究结果表明，一氧化氮是新生神经元中受神经营养因子信号刺激的旁分泌信使，控制鼻咽癌的增殖和分化，是调节发育和成人神经发生的新机制。(C) 2003 Elsevier Science（美国）版权所有。
Nitric oxide (NO) is believed to act as an intercellular signal that regulates synaptic plasticity in mature neurons. We now report that NO also regulates the proliferation and differentiation of mouse brain neural progenitor cells (NPCs). Treatment of dissociated mouse cortical neuroepithelial cluster cell cultures with the NO synthase inhibitor L-NAME or the NO scavenger hemoglobin increased cell proliferation and decreased differentiation of the NPCs into neurons, whereas the NO donor sodium nitroprusside inhibited NPC proliferation and increased neuronal differentiation. Brain-derived neurotrophic factor (BDNF) reduced NPC proliferation and increased the expression of neuronal NO synthase (nNOS) in differentiating neurons. The stimulatory effect of BDNF on neuronal differentation of NPC was blocked by L-NAME and hemoglobin, suggesting that NO produced by the latter cells inhibited proliferation and induced neuronal differentiation of neighboring NPCs. A similar role for NO in regulating the switch of neural stem cells from proliferation to differentiation in the adult brain is suggested by data showing that NO synthase inhibition enhances NPC proliferation and inhibits neuronal differentiation in the subventricular zone of adult mice. These findings identify NO as a paracrine messenger stimulated by neurotrophin signaling in newly generated neurons to control the proliferation and differentiation of NPC, a novel mechanism for the regulation of developmental and adult neurogenesis. (C) 2003 Elsevier Science (USA). All rights reserved.