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首页> 外文期刊>Translational Developmental Psychiatry >Effects of Acute Tryptophan Depletion on Brain Serotonin Function and Concentrations of Dopamine and Norepinephrine in C57BL/6J and BALB/cJ Mice
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Effects of Acute Tryptophan Depletion on Brain Serotonin Function and Concentrations of Dopamine and Norepinephrine in C57BL/6J and BALB/cJ Mice

机译:急性色氨酸耗竭对C57BL / 6J和BALB / cJ小鼠脑5-羟色胺功能及多巴胺和去甲肾上腺素浓度的影响

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BackgroundAcute tryptophan depletion (ATD) is a method of lowering brain serotonin (5-HT) synthesis. Administration of large neutral amino acids (LNAA) limits the transport of endogenous tryptophan (TRP) across the blood–brain barrier by competition with other LNAAs and subsequently decreases serotonergic neurotransmission. A recent discussion on the specificity and efficacy of the ATD paradigm for inhibition of central nervous 5-HT has arisen. ATD Moja-De is a revised mixture of AAs which is less nauseating than conventional protocols, possibly because of an administration in accordance with the body weight of the subjects. It has been used in the preliminary clinical studies, but its effects on central 5-HT mechanisms and other neurotransmitter systems have not been validated in an animal model.DesignWe tested ATD Moja-De (TRP-) in two strains of mice, C57BL/6 and BALB/cJ, which are reported to have impaired 5-HT synthesis relative to other strains of mice.ResultsATD Moja-De lowered brain TRP, significantly decreased central nervous 5-HT synthesis as indexed by 5-HTP levels after decarboxlyase inhibition, and lowered 5-HT and 5 HIAA in both strains of mice, however, more so in C57 BL/6 than in BALB/cJ. Dopamine and its metabolites as well as norepinephrine were not affected. A tryptophan-balanced control mixture did not increase 5-HT or 5-HIAA.ConclusionThe present findings suggest that ATD Moja-De effectively suppresses central serotonergic function, and that the effects of ATD Moja-De are specific to serotonin function.
机译:背景急性色氨酸耗竭(ATD)是一种降低脑5-羟色胺(5-HT)合成的方法。通过与其他LNAA竞争,大中性氨基酸(LNAA)的施用限制了内源性色氨酸(TRP)跨血脑屏障的运输,从而降低了血清素能神经传递。最近出现了有关ATD范式抑制中枢神经5-HT的特异性和功效的讨论。 ATD Moja-De是AA的改良混合物,它比常规方案少令人恶心,这可能是因为根据受试者的体重进行的给药。它已用于初步临床研究中,但尚未在动物模型中验证其对中枢5-HT机制和其他神经递质系统的影响。设计我们在两种小鼠C57BL /小鼠中测试了ATD Moja-De(TRP-)。 6和BALB / cJ,据报道相对于其他小鼠品系而言,5-HT合成受损。结果ATD Moja-De降低了脑TRP,显着降低了中枢神经5-HT合成,如通过去羧酶抑制后5-HTP水平所指示的,并且降低了两种小鼠品系中的5-HT和5 HIAA,但是,在C57 BL / 6中比在BALB / cJ中降低更多。多巴胺及其代谢产物以及去甲肾上腺素不受影响。色氨酸平衡的对照混合物不会增加5-HT或5-HIAA。结论本研究结果表明ATD Moja-De有效抑制了中枢5-羟色胺功能,而ATD Moja-De的作用对血清素功能具有特异性。

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