Bilobalide modulates serotonin-controlled behaviors in the nematode Caenorhabditis elegans.
Bilobalide modulates serotonin-controlled behaviors in the nematode Caenorhabditis elegans.
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DOI：
10.1186/1471-2202-10-62
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发表时间：
2009-06-22
期刊：
影响因子：
2.4
通讯作者：
Luo Y
中科院分区：
文献类型：
--
作者：
Brown MK;Luo Y
血清素能系统的功能障碍与抑郁症等几种神经系统疾病有关。被诊断为临床抑郁症的老年人显示出神经退行性疾病的增加。这提示调节5-羟色胺（5-HT）系统可以提供一种替代当前治疗的方法来减轻这些病理。双叶碱在体外的神经保护作用已被证实。我们的目的是确定双胆碱是否影响线虫的5-羟色胺系统。研究人员给野生型蠕虫和具有良好特征的5-HT突变体喂食不同浓度的双叶碱，并测试了几种5-HT控制行为。我们观察到双胆碱能以剂量依赖的方式显著抑制5-HT控制的产卵行为，这在5-HT受体突变体（ser-4, mod-1）中被阻断，但在5-HT转运体（mod-5）或合成（tph-1）突变体中不被阻断。双胆碱还增强了5- ht控制的、经验依赖的运动行为，称为野生型动物的增强慢反应。然而，这种作用在5-HT受体mod-1和多巴胺缺陷猫-2突变体中被完全阻断，而在ser-4突变体中仅部分阻断。我们还证明了乙酰胆碱在组成性表达a β的转基因秀丽隐杆线虫菌株中被抑制，而双胆碱对这种抑制作用没有显著影响。这些结果表明双胆碱可能调节特定的5-HT受体亚型，这涉及到与多巴胺传递的相互作用。对双胆碱在神经递质系统中的功能的进一步研究有助于我们了解其神经保护特性。
Dysfunctions in the serotonergic system have been implicated in several neurological disorders such as depression. Elderly individuals who have been diagnosed with clinical depression show elevated cases of neurodegenerative diseases. This has led to suggestions that modulating the serotonin (5-HT) system could provide an alternative method to current therapies for alleviating these pathologies. The neuroprotective effects of bilobalide in vitro have been documented. We aim to determine whether bilobalide affects the 5-HT system in the nematode C. elegans. The wild type worms, as well as well-characterized 5-HT mutants, were fed with bilobalide in a range of concentrations, and several 5-HT controlled behaviors were tested. We observed that bilobalide significantly inhibited 5-HT-controlled egg-laying behavior in a dose-dependent manner, which was blocked in the 5-HT receptor mutants (ser-4, mod-1), but not in the 5-HT transporter (mod-5) or synthesis (tph-1) mutants. Bilobalide also potentiated a 5-HT-controlled, experience-dependent locomotory behavior, termed the enhanced slowing response in the wild type animals. However, this effect was fully blocked in 5-HT receptor mod-1 and dopamine defective cat-2 mutants, but only partially blocked in ser-4 mutants. We also demonstrated that acetylcholine transmission was inhibited in a transgenic C. elegans strain that constitutively expresses Aβ, and bilobalide did not significantly affect this inhibition. These results suggest that bilobalide may modulate specific 5-HT receptor subtypes, which involves interplay with dopamine transmission. Additional studies for the function of bilobalide in neurotransmitter systems could aid in our understanding of its neuroprotective properties.
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