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Alterations on the morphology, nitric oxide synthesis and activity of platelets reproduced in rats as possible biomarkers for depression are reversed by fluoxetine

机译:氟西汀逆转了大鼠形态学,一氧化氮合成和血小板活性的改变,这可能是抑郁症的生物标志物

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Biochemical markers associated with the prognosis of depression in humans are being described in the literature, whereas experimental studies in animal models in search for antidepressant strategies are lacking. The aim of this study was to evaluate platelet morphology, platelet activity and nitric oxide (NO) synthesis as possible biomarkers of depressive-like behavior by using FST alone and in the presence of fluoxetine. Na?ve rats were compared to those receiving vehicle or fluoxetine at 10 mg/kg i.p. in acute, subchronic and chronic administration in the FST. After behavioral assessment, platelets were isolated from blood samples and analyzed by flow cytometry to determine the platelet mitochondrial membrane potential and NO synthesis. In addition, HPLC and electron microscopy were used to examine 5-HT and tryptophan levels and morphology of platelets, respectively. Rats receiving vehicle and exposed to FST showed depressive-like behavior at all the times tested; after chronic FST rats showed a similar pattern of alteration in platelet morphology and in the studied as possible biochemical markers as those previously recognized in depressive humans. Depressive-like behavior in rats exposed to FST was prevented in the presence of fluoxetine administration at all the times tested and associated with the prevention of alterations in platelet morphology, platelet activity and NO synthesis, and/or in 5-HT concentrations. The results of the present study suggest that platelet function and morphology might be relevant markers for the prognosis of depression and the search for functional treatments. Besides, the relevance of FST as model to study this psychiatric illness is reinforced.
机译:文献中描述了与人类抑郁预后相关的生物化学标记,而缺乏在动物模型中寻找抗抑郁策略的实验研究。这项研究的目的是通过单独使用FST和在氟西汀的存在下评估血小板形态,血小板活性和一氧化氮(NO)合成作为抑郁样行为的可能生物标志物。将幼稚大鼠与接受媒介物或氟西汀10毫克/千克腹腔注射的大鼠进行比较。在FST的急性,亚慢性和慢性管理中。进行行为评估后,从血液样本中分离出血小板,并通过流式细胞仪进行分析,以确定血小板的线粒体膜电位和NO的合成。另外,HPLC和电子显微镜分别用于检查5-HT和色氨酸水平以及血小板形态。接受赋形剂并暴露于FST的大鼠在所有测试时间均表现出抑郁样行为。在慢性FST大鼠中,血小板显示出相似的变化形态,并且在研究的可能的生化标记中与先前在抑郁症人类中所识别的相似。在所有测试的时间中,都在氟西汀的存在下预防了暴露于FST的大鼠的抑郁样行为,并且与预防血小板形态,血小板活性和NO合成和/或5-HT浓度的改变有关。本研究结果表明,血小板功能和形态可能是抑郁症预后和寻找功能性治疗的相关标志。此外,FST作为研究这种精神疾病模型的相关性得到了加强。

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