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Inhibitory effect of dehydroepiandrosterone on brain monoamine oxidase activity: in vivo and in vitro studies.

机译:脱氢表雄酮对脑单胺氧化酶活性的抑制作用:体内和体外研究。

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AIMS: To evaluate the acute effect of dehydroepiandrosterone (DHEA) on monoamine oxidase (MAO) activity in the corpus striatum (CS) and the nucleus accumbens (NAc) in vivo and in vitro. MAIN METHODS: Male Wistar rats received an i.p. injection of DHEA (30, 60 and 120mg/kg) and MAO activity was assayed by formation of 4-hydroxyquinoline 2h later. For in vitro studies, DHEA (100nM-1mM) was added to brain tissue homogenates to assay MAO activity. KEY FINDINGS: DHEA significantly reduced (-24%) total MAO activity in the NAc (F=8.5, p<0.001), but not in the CS, at 120mg/kg dose. No significant difference was observed when MAO A and MAO B activities were independently analyzed. When assayed in vitro, total MAO, MAO A and MAO B activities were reduced by DHEA to 55.7, 28.2 and 54.4% in the NAc and to 71.9, 44.2 and 61.2% in the CS, respectively (IC(50) 4.7-56.1microM). SIGNIFICANCE: An inhibitory effect of DHEA on MAO activity may be involved in the antidepressant and neuroprotective effects of the steroid. Since MAO inhibition reduces neurodegeneration in clinical trials for Parkinson's disease, our results suggest that DHEA may be useful to treat depression and to prevent neuronal death in this disorder.
机译:目的:评价脱氢表雄酮(DHEA)对体内和体外纹状体(CS)和伏隔核(NAc)中单胺氧化酶(MAO)活性的急性影响。主要方法:雄性Wistar大鼠接受腹腔注射。注射脱氢表雄酮(DHEA)(30、60和120mg / kg),并在2h后通过形成4-羟基喹啉来测定MAO活性。对于体外研究,将DHEA(100nM-1mM)添加到脑组织匀浆中以测定MAO活性。主要发现:在120mg / kg剂量下,DHEA显着降低了NAc中总MAO活性(-24%)(F = 8.5,p <0.001),而CS中未降低。独立分析MAO A和MAO B活性时,未观察到显着差异。体外测定时,DHEA分别将总MAO,MAO A和MAO B活性分别降低至NAc的55.7%,28.2%和54.4%,CS的71.9%,44.2%和61.2%(IC(50)4.7-56.1microM )。意义:DHEA对MAO活性的抑制作用可能与类固醇的抗抑郁和神经保护作用有关。由于在针对帕金森氏病的临床试验中,MAO抑制作用可减少神经退行性变,因此我们的结果表明DHEA可能可用于治疗该疾病的抑郁症和预防神经元死亡。

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