Fluoxetine regulates the expression of neurotrophic/growth factors and glucose metabolism in astrocytes
Fluoxetine regulates the expression of neurotrophic/growth factors and glucose metabolism in astrocytes
复制标题
DOI：
10.1007/s00213-011-2190-y
复制
发表时间：
2011-07-01
影响因子：
3.4
通讯作者：
Martin, Jean-Luc
中科院分区：
文献类型：
--
作者：
Allaman, Igor;Fiumelli, Hubert;Martin, Jean-Luc
基本原理大多数抗抑郁药的药理作用归因于脑中肾上腺素能和/或去甲肾上腺素能传递的调节。在重度抑郁症的治疗过程中，最常用的选择性5-羟色胺再摄取抑制剂（SSRI）抗抑郁药之一氟西汀在大脑中蓄积，表明氟西汀可能与其他靶点相互作用。在这种情况下，有越来越多的证据表明，星形胶质细胞参与的病理生理学的主要depression.Objectives本研究的目的是研究氟西汀对表达的神经营养/生长因子，具有抗抑郁性质和对葡萄糖代谢的影响，在培养的皮质星形胶质细胞。上调脑源性神经营养因子（BDNF）、血管内皮生长因子（VEGF）和VGF mRNA表达。相反，三环类抗抑郁药地昔帕明和丙咪嗪不影响这些神经营养/生长因子的表达。氟西汀对葡萄糖代谢影响的分析显示，氟西汀可降低糖原水平，增加星形胶质细胞的葡萄糖利用率和乳酸释放。帕罗西汀也获得了类似的数据，而丙咪嗪和地昔帕明并不调节该胶质细胞群的葡萄糖代谢。我们的研究结果还表明，氟西汀和帕罗西汀对葡萄糖利用率，乳酸释放，和BDNF，VEGF和VGF的表达的影响是不介导的阿托伐他汀依赖mechanism.Conclusions这些数据表明，通过增加特定的星形胶质细胞源性神经营养因子的表达和从星形胶质细胞释放乳酸，氟西汀可能有助于正常化的营养和代谢支持神经元在抑郁症。
Rationale The pharmacological actions of most antidepressants are ascribed to the modulation of serotonergic and/or noradrenergic transmission in the brain. During therapeutic treatment for major depression, fluoxetine, one of the most commonly prescribed selective serotonin reuptake inhibitor (SSRI) antidepressants, accumulates in the brain, suggesting that fluoxetine may interact with additional targets. In this context, there is increasing evidence that astrocytes are involved in the pathophysiology of major depression.Objectives The aim of this study was to examine the effects of fluoxetine on the expression of neurotrophic/growth factors that have antidepressant properties and on glucose metabolism in cultured cortical astrocytes.Results Treatment of astrocytes with fluoxetine and paroxetine, another SSRI antidepressant, upregulated brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and VGF mRNA expression. In contrast, the tricyclic antidepressants desipramine and imipramine did not affect the expression of these neurotrophic/growth factors. Analysis of the effects of fluoxetine on glucose metabolism revealed that fluoxetine reduces glycogen levels and increases glucose utilization and lactate release by astrocytes. Similar data were obtained with paroxetine, whereas imipramine and desipramine did not regulate glucose metabolism in this glial cell population. Our results also indicate that the effects of fluoxetine and paroxetine on glucose utilization, lactate release, and expression of BDNF, VEGF, and VGF are not mediated by serotonin-dependent mechanisms.Conclusions These data suggest that, by increasing the expression of specific astrocyte-derived neurotrophic factors and lactate release from astrocytes, fluoxetine may contribute to normalize the trophic and metabolic support to neurons in major depression.