Chronic olanzapine or fluoxetine administration increases cell proliferation in hippocampus and prefrontal cortex of adult rat
Chronic olanzapine or fluoxetine administration increases cell proliferation in hippocampus and prefrontal cortex of adult rat
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DOI：
10.1016/j.biopsych.2004.07.008
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发表时间：
2004-10-15
影响因子：
10.6
通讯作者：
Duman, RS
中科院分区：
文献类型：
--
作者：
Kodamo, M;Fujioko, T;Duman, RS
背景资料：有越来越多的证据表明，非典型抗精神病药物是有效的治疗情绪障碍或增强5-羟色胺选择性再摄取抑制剂治疗难治性depression.Methods：上调神经发生在成年海马是一个标记的抗抑郁活性，和本研究调查的非典型抗精神病药物奥氮平对细胞增殖的影响在成年大鼠海马。成年大鼠的前边缘皮层的细胞增殖的调节也examined.Results：慢性（21天）奥氮平给药增加了新生细胞的数量在海马齿状回的氟西汀相同的程度。奥氮平或氟西汀治疗也增加了前边缘皮质中增殖细胞的数量。相比之下，在室管膜下区或初级运动皮层中没有任何药物的作用，并且在纹状体中有增加的趋势。奥氮平亚慢性（7天）给药对海马或前边缘皮质的细胞增殖没有影响，与氟西汀作用的时间过程和抗抑郁治疗的治疗作用一致。奥氮平加氟西汀联合治疗在两个脑区均未导致更大的细胞增殖诱导。细胞表型的分析表明，在前边缘皮质中大约20%的新生细胞分化为内皮细胞，但不是神经元，与齿状回相反，在齿状回中大多数新生细胞分化为神经元。结果表明，抗抑郁药或非典型抗精神病药物可以增加边缘脑结构中神经胶质的增殖，这种效果可以逆转在抑郁症患者中观察到的神经胶质细胞的丧失。
Background: There has been increasing evidence that atypical antipsychotics are effective in the treatment of mood disorders or for augmenting 5-hydroxytryptamine selective reuptake inhibitors for treatment-resistant depression.Methods: Upregulation of neurogenesis in the adult hippocampus is a marker of antidepressant activity, and the present study investigated the influence of the atypical antipsychotic drug olanzapine on cell proliferation in the hippocampus of adult rat. The regulation of cell proliferation in the prelimbic cortex of adult rat was also examined.Results: Chronic (21 days) olanzapine administration increased the number of newborn cells in the dentate gyrus of the hippocampus to the same extent as fluoxetine. Olanzapine or fluoxetine treatment also increased the number of proliferating cells in the prelimbic cortex. In contrast, there was no effect of either drug in the subventricular zone or primary motor cortex, and there was a trend for an increase in the striatum. Subchronic (7 days) administration of olanzapine had no effect on cell proliferation in hippocampus or prelimbic cortex, consistent with the time course for the effect of fluoxetine and the therapeutic actions of antidepressant treatment. The combination of olanzapine plus fluoxetine did not result in a greater induction of cell proliferation in either brain region. Analysis of the cell phenotype demonstrated that approximately 20% of the newborn cells in the prelimbic cortex differentiated into endothelial cells but not neurons, in contrast to the dentate gyrus, where most newborn cells differentiated into neurons.Conclusions: The results demonstrate that antidepressant or atypical antipsychotic medications can increase the proliferation of glia in limbic brain structures, an effect that could reverse the loss of glia that has been observed in depressed patients.