Fluoxetine targets early progenitor cells in the adult brain
Fluoxetine targets early progenitor cells in the adult brain
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DOI：
10.1073/pnas.0601992103
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发表时间：
2006-05-23
影响因子：
11.1
通讯作者：
Enikolopov, Grigori
中科院分区：
文献类型：
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作者：
Encinas, Juan M.;Vaahtokari, Anne;Enikolopov, Grigori
抗抑郁药慢性治疗增加成年海马神经发生。这种新神经元产生的增加可能是抗抑郁药的行为效应所必需的。然而，尚不清楚药物靶向神经元分化级联中的哪一类细胞。我们已经产生了一个报告小鼠系，它允许早期神经元祖细胞的识别和分类。它还允许准确定量的变化诱导的神经原性药物在这些不同的神经元前体亚类。我们使用这条线来证明选择性5-羟色胺再摄取抑制剂抗抑郁药氟西汀不影响齿状回中干细胞样细胞的分裂，但增加早期祖细胞类的对称分裂。我们进一步证明，这些细胞是唯一一类的神经元祖细胞的氟西汀在成人大脑中的目标，并建议氟西汀诱导的增加，在新的神经元出现作为结果的扩展，这类细胞。这一发现定义了抗抑郁药物治疗的细胞靶点。
Chronic treatment with antidepressants increases neurogenesis in the adult hippocampus. This increase in the production of new neurons may be required for the behavioral effects of antidepressants. However, it is not known which class of cells within the neuronal differentiation cascade is targeted by the drugs. We have generated a reporter mouse line, which allows identification and classification of early neuronal progenitors. It also allows accurate quantitation of changes induced by neurogenic agents in these distinct subclasses of neuronal precursors. We use this line to demonstrate that the selective serotonin reuptake inhibitor antidepressant fluoxetine does not affect division of stem-like cells in the dentate gyrus but increases symmetric divisions of an early progenitor cell class. We further demonstrate that these cells are the sole class of neuronal progenitors targeted by fluoxetine in the adult brain and suggest that the fluoxetine-induced increase in new neurons arises as a result of the expansion of this cell class. This finding defines a cellular target for antidepressant drug therapies.