Activation of NMDA receptors increases proliferation and differentiation of hippocampal neural progenitor cells
Activation of NMDA receptors increases proliferation and differentiation of hippocampal neural progenitor cells
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DOI：
10.1242/jcs.002154
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发表时间：
2007-04-15
影响因子：
4
通讯作者：
Son, Hyeon
中科院分区：
文献类型：
--
作者：
Joo, Jae-Yeol;Kim, Byung-Woo;Son, Hyeon
本实验观察了N-甲基-D-天冬氨酸（NMDA）受体激活对海马神经前体细胞（NPC）增殖和分化的长期影响。在有丝分裂原介导的增殖条件下，单次NMDA脉冲（5 μ M）在延迟72小时后增加了5-溴-2-脱氧尿苷（BrdU）阳性（BrdU（+））细胞的分数.同样，单次全身注射NMDA（100 mg/ kg）28天后，齿状回（DG）中BrdU（+）细胞的数量增加，但3天后没有。NMDA受体激活诱导Ca 2+立即流入NPC，并且NPC在72小时内以NMDA受体依赖性方式表达并释放血管内皮生长因子（VEGF）。在相同剂量的重复刺激下，NMDA刺激获得神经元表型，伴随着前神经元碱性螺旋-环-螺旋（bHLH）因子表达的增加。总之，这些研究结果表明，在发育中的大脑中的神经发生可能是直接和间接调节的复杂的相互作用之间的Ca 2+流入和兴奋释放的细胞因子，即使在温和的兴奋水平。此外，我们的研究结果是第一次表明，刺激NPC可能会导致增殖或神经元分化，这取决于NMDA受体激活的水平。
The prolonged effects of N-methyl-D-aspartate ( NMDA) receptor activation on the proliferation and differentiation of hippocampal neural progenitor cells (NPCs) were studied. Under conditions of mitogen- mediated proliferation, a single NMDA pulse ( 5 mu M) increased the fraction of 5- bromo- 2- deoxyuridine ( BrdU)-positive ( BrdU(+)) cells after a delay of 72 hours. Similarly, a single systemic injection of NMDA ( 100 mg/ kg) increased the number of BrdU(+) cells in the dentate gyrus ( DG) after 28 days, but not after 3 days. NMDA receptor activation induced an immediate influx of Ca2+ into the NPCs and the NPCs expressed and released vascular endothelial growth factor ( VEGF) in an NMDA receptor- dependent manner within 72 hours. With repetitive stimulation at the same dose, NMDA stimulated the acquisition of a neuronal phenotype accompanied by an increase in the expression of proneural basic helix-loop-helix ( bHLH) factors. Together these findings suggest that neurogenesis in the developing brain is likely to be both directly and indirectly regulated by complex interactions between Ca2+ influx and excitation-releasable cytokines, even at mild levels of excitation. In addition, our results are the first to show that stimulation of NPCs may lead to either proliferation or neuronal differentiation, depending on the level of NMDA receptor activation.