Fluoxetine Administration Modulates the Cytoskeletal Microtubular System in the Rat Hippocampus
Fluoxetine Administration Modulates the Cytoskeletal Microtubular System in the Rat Hippocampus
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DOI：
10.1002/syn.20614
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发表时间：
2009-04-01
期刊：
影响因子：
2.3
通讯作者：
Marsden, Charles A.
中科院分区：
文献类型：
--
作者：
Bianchi, Massimiliano;Shah, Ajit J.;Marsden, Charles A.
许多研究表明，压力条件可以诱导海马结构的改变，抗抑郁药物可以防止这种缺陷。特别是，选择性5-羟色胺再摄取抑制剂（SSRI）氟西汀更有效地调节不同的神经元可塑性现象和相关分子在大鼠海马。细胞骨架微管动力学是树突和轴突重塑的基础，导致氟西汀可能影响微管系统的假设。然而，尽管报告的压力引起的微管动力学的改变，不同的压力，只有少数研究调查在体内的影响和抑制剂对微管在特定的大鼠大脑区域。本研究调查了剂量相关（1、5或10 mg/kg i.p.）氟西汀的急性和慢性（21天）治疗对海马α-微管蛋白同种型比率的影响，认为其反映微管动力学。蛋白质印迹分析用于定量α-微管蛋白亚型，高效液相色谱和荧光检测用于测量离体单胺代谢。结果表明，急性氟西汀增加了稳定形式的乙酰化和脱酪氨酸α-微管蛋白。相反，慢性氟西汀降低乙酰化α-微管蛋白，表明微管动力学增加。神经元特异性Δ 2-微管蛋白在慢性氟西汀作用下增加，表明神经元参与了观察到的细胞骨架变化。尽管急性和慢性氟西汀通过抑制5-羟色胺再摄取类似地改变了5-羟色胺代谢，但这与细胞骨架扰动无明显相关性。我们的研究结果表明，氟西汀管理调节大鼠海马微管动力学。氟西汀所产生的细胞骨架效应可能最终导致促进结构神经元重塑的事件。Synapse 63：359 - 364，2009. (c)2009威利-利斯公司
A number of studies suggest that stressful conditions can induce structural alterations in the hippocampus and that antidepressant drugs may prevent such deficits. In particular, the selective serotonin reuptake inhibitor (SSRI) fluoxetine was more effective in modulating different neuronal plasticity phenomena and related molecules in rat hippocampus. Cytoskeletal microtubule dynamics are fundamental to dendrites and axons remodeling, leading to the hypothesis that fluoxetine may affect the microtubular system. However, despite reports of stress-induced alterations in microtubule dynamics by different stressors, only few studies investigated the in vivo effects of and depressants on microtubules in specific rat brain regions. The present study investigated the dose-related (1, 5, or 10 mg/kg i.p.) effects of acute and chronic (21 days) treatments with fluoxetine on the ratio of hippocampal alpha-tubulin isoforms which is thought to reflect microtubule dynamics. Western Blot analysis was used to quantify alpha-tubulin isoforms, high-performance liquid chromatography and fluorescence detection was used to measure ex vivo monoamine metabolism. The results showed that acute fluoxetine increased the stable forms acetylated and detyrosinated alpha-tubulin. Conversely, chronic fluoxetine decreased acetylated alpha-tubulin, indicative of increased microtubule dynamics. The neuron-specific Delta 2-Tubulin was increased by chronic fluoxetine indicating neuronal involvement in the observed cytoskeletal changes, Although acute and chronic fluoxetine similarly altered serotonin metabolism by inhibition of serotonin reuptake, this showed no apparent correlation to the cytoskeletal perturbations. Our findings demonstrate that fluoxetine administration modulates microtubule dynamics in rat hippocampus. The cytoskeletal effect exerted by fluoxetine may eventually culminate in promoting events of structural neuronal remodeling. Synapse 63:359-364, 2009. (c) 2009 Wiley-Liss, Inc.