Antidepressant effects of crocin and its effects on transcript and protein levels of CREB, BDNF, and VGF in rat hippocampus.

Antidepressant effects of crocin and its effects on transcript and protein levels of CREB, BDNF, and VGF in rat hippocampus.
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DOI:
10.1186/2008-2231-22-16
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发表时间:
2014-01-08
期刊:
Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences
影响因子:
--
通讯作者:
Hosseinzadeh H
Hosseinzadeh H
中科院分区:
其他
文献类型:
--
作者:
Vahdati Hassani F;Naseri V;Razavi BM;Mehri S;Abnous K;Hosseinzadeh H

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抗抑郁药已被证明会影响脑源性神经营养因子(BDNF)和VGF(非首字母缩写)的水平,在长期治疗中,它们的转录依赖于cAMP反应元件结合蛋白(CREB)。本研究的目的是验证藏红花(Crocus sativus L.)的活性成分藏红花素的亚急性抗抑郁作用,及其对大鼠海马中CREB、BDNF和VGF蛋白、转录水平和活性磷酸化CREB(P-CREB)蛋白量的影响。将藏红花素(12.5、25和50 mg/kg)、丙咪嗪(10 mg/kg;阳性对照)和盐水(1 mL/kg;中性对照)腹膜内(IP)给予雄性Wistar大鼠21天。注射后第21天,采用强迫游泳试验(FST)研究抗抑郁作用。分别采用蛋白质印迹和定量逆转录聚合酶链反应(qRT-PCR)评价大鼠海马中蛋白质表达和基因转录水平。西红花苷显著减少了FST中的不动时间。Western blot分析表明,25和50 mg/kg西红花苷显著增加CREB和BDNF的水平,并呈剂量依赖性。所有剂量的西红花苷以剂量依赖性方式增加VGF水平。50 mg/kg剂量的西红花苷使p-CREB水平显著增加。只有12.5mg/kg西红花苷能显著提高BDNF的转录水平。CREB和VGF转录水平在所有组中均未观察到变化。这些结果表明,西红花苷具有抗抑郁样作用,通过增加海马CREB,BDNF和VGF水平。
Antidepressants have been shown to affect levels of brain-derived neurotrophic factor (BDNF) and VGF (non-acronymic) whose transcriptions are dependent on cAMP response element binding protein (CREB) in long term treatment. The aim of this study was to verify the subacute antidepressant effects of crocin, an active constituent of saffron (Crocus sativus L.), and its effects on CREB, BDNF, and VGF proteins, transcript levels and amount of active, phosphorylated CREB (P-CREB) protein in rat hippocampus. Crocin (12.5, 25, and 50 mg/kg), imipramine (10 mg/kg; positive control) and saline (1 mL/kg; neutral control) were administered intraperitoneally (IP) to male Wistar rats for 21 days. The antidepressant effects were studied using the forced swimming test (FST) on day 21 after injection. Protein expression and transcript levels of genes in the rat hippocampus were evaluated using western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), respectively. Crocin significantly reduced the immobility time in the FST. Western blot analysis showed that 25 and 50 mg/kg of crocin increased the levels of CREB and BDNF significantly and dose dependently. All doses of crocin increased the VGF levels in a dose-dependent manner. Levels of p-CREB increased significantly by 50 mg/kg dose of crocin. Only 12.5 mg/kg crocin could significantly increase the transcript levels of BDNF. No changes in CREB and VGF transcript levels were observed in all groups. These results suggest that crocin has antidepressant-like action by increasing CREB, BDNF and VGF levels in hippocampus.
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