VEGF is an essential mediator of the neurogenic and behavioral actions of antidepressants
VEGF is an essential mediator of the neurogenic and behavioral actions of antidepressants
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DOI：
10.1073/pnas.0610282104
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发表时间：
2007-03-13
影响因子：
11.1
通讯作者：
Duman, Ronald S.
中科院分区：
文献类型：
--
作者：
Warner-Schmidt, Jennifer L.;Duman, Ronald S.
抗抑郁药在细胞和行为方面的反应所依赖的神经机制尚不明确。生长因子的上调以及成年神经发生表明这些因子中的一种或多种在抗抑郁药的作用中起作用。一个令人感兴趣的候选因子是血管内皮生长因子（VEGF），它最初因其在血管生成中的作用而被确定特征，但在体外也对神经祖细胞产生直接的促有丝分裂作用。这项研究的结果表明，多种类型的抗抑郁药在与这些治疗诱导细胞增殖和治疗作用相一致的时间点诱导VEGF。我们发现通过Flk - 1受体的VEGF信号传导是抗抑郁药诱导细胞增殖所必需的。我们还表明，在两种慢性和两种亚慢性抗抑郁模型中，VEGF - Flk - 1信号传导对于行为反应是必需的且是足够的。综上所述，这些研究确定VEGF和VEGF - Flk - 1信号传导是抗抑郁作用的介质以及治疗干预的潜在靶点。
The neural mechanisms underlying the cellular and behavioral responses to antidepressants are not yet, known. Up-regulation of growth factors and adult neurogenesis suggest a role for one or more of these factors in the action of antidepressants. One candidate of interest is vascular endothelial growth factor (VEGF), which was initially characterized for its role in angiogenesis, but also exerts direct mitogenic effects on neural progenitors in vitro. Results of this study demonstrate that VEGF is induced by multiple classes of antidepressants at time points consistent with the induction of cell proliferation and therapeutic action of these treatments. We find that VEGF signaling through the Flk-1 receptor is required for antidepressant-induced cell proliferation. We also show that VEGF-Flk-1 signaling is required and sufficient for behavioral responses in two chronic and two subchronic antidepressant models. Taken together, these studies identify VEGF and VEGF-Flk-1 signaling as mediators of antidepressant actions and potential targets for therapeutic intervention.