Electroconvulsive seizure and VEGF increase the proliferation of neural stem-like cells in rat hippocampus
Electroconvulsive seizure and VEGF increase the proliferation of neural stem-like cells in rat hippocampus
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DOI：
10.1073/pnas.0710858105
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发表时间：
2008-08-12
影响因子：
11.1
通讯作者：
Duman, Ronald S.
中科院分区：
文献类型：
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作者：
Segi-Nishida, Eri;Warner-Schmidt, Jennifer L.;Duman, Ronald S.
所有类别的抗抑郁药都会增加海马细胞增殖和神经发生，这在一定程度上有助于这些治疗的行为作用。在抗抑郁治疗中，电惊厥发作（ECS）是海马细胞增殖最强有力的刺激剂，也是治疗抑郁症最有效的方法，但 ECS 作用的细胞机制尚不清楚。为了解决这个问题，我们研究了 ECS 对大鼠齿状回颗粒下区神经干细胞样和/或祖细胞增殖的影响。我们通过选择性细胞和有丝分裂活性标记物的共表达来定义从干细胞样细胞到早期神经祖细胞（也分别称为静态和扩增神经祖细胞）的神经分化级联。我们发现，在有丝分裂早期，ECS 增加了静止祖细胞的增殖，然后在后期增加了扩增祖细胞的增殖。我们进一步证明，血管内皮生长因子 (VEGF) 信号传导对于 ECS 诱导静止神经祖细胞增殖是必需的，并且足以产生这种效果。这些发现表明，ECS 和随后的 VEGF 诱导刺激神经干样细胞和神经祖细胞的增殖，从而解释了 ECS 与化学抗抑郁药相比具有优越的神经源性作用。
All classes of antidepressants increase hippocampal cell proliferation and neurogenesis, which contributes, in part, to the behavioral actions of these treatments. Among antidepressant treatments, electroconvulsive seizure (ECS) is the most robust stimulator of hippocampal cell proliferation and the most efficacious treatment for depression, but the cellular mechanisms underlying the actions of ECS are unknown. To address this question, we investigated the effect of ECS on proliferation of neural stem-like and/or progenitor cells in the subgranular zone of rat dentate gyrus. We define the neural differentiation cascade from stem-like cells to early neural progenitors (also referred to as quiescent and amplifying neural progenitors, respectively) by co-expression of selective cellular and mitotic activity markers. We find that at an early mitotic phase ECS increases the proliferation of quiescent progenitors and then at a later phase increases the proliferation of amplifying progenitors. We further demonstrate that vascular endothelial growth factor (VEGF) signaling is necessary for ECS induction of quiescent neural progenitor cell proliferation and is sufficient to produce this effect. These findings demonstrate that ECS and subsequent induction of VEGF stimulates the proliferation of neural stem-like cells and neural progenitor cells, thereby accounting for the superior neurogenic actions of ECS compared with chemical antidepressants.