Dopamine Modulates Serotonin Innervation in the Drosophila Brain.
Dopamine Modulates Serotonin Innervation in the Drosophila Brain.
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DOI：
10.3389/fnsys.2017.00076
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发表时间：
2017
影响因子：
3
通讯作者：
Riemensperger TD
中科院分区：
文献类型：
--
作者：
Niens J;Reh F;Çoban B;Cichewicz K;Eckardt J;Liu YT;Hirsh J;Riemensperger TD
帕金森病（PD）是由多巴胺能黑质纹状体系统的进行性变性引起的，其导致运动控制下降，伴有静止性震颤、僵硬和姿势不稳定。PD的几个方面可以在果蝇（Drosophila melanogaster）中建模，包括α-突触核蛋白诱导的多巴胺能神经元变性，或神经DA合成的遗传消除导致的多巴胺（DA）丢失。后一种模型中的缺陷行为可以通过喂食DA前体L-DOPA来改善，类似于PD的治疗范例。PD患者中L-DOPA治疗的继发性并发症与5-羟色胺（5-HT）释放神经元中DA的异位合成相关，导致DA/5-HT失衡。在这里，我们研究了神经解剖学的适应造成不平衡的DA/5-HT信号在果蝇突变体缺乏神经DA。我们发现，类似于啮齿动物模型的PD，缺乏DA导致增加5-HT水平和arborizations在特定的大脑区域。相反，通过L-DOPA喂养增加的DA水平导致蘑菇体（MB）中5-HT神经元与其靶神经元的连接性降低。所观察到的5-HT神经元可塑性的改变表明，DA信号的损失是不是唯一负责在果蝇模型中观察到的PD的行为障碍，而是后者的组合与5-HT电路的改变。
Parkinson’s disease (PD) results from a progressive degeneration of the dopaminergic nigrostriatal system leading to a decline in movement control, with resting tremor, rigidity and postural instability. Several aspects of PD can be modeled in the fruit fly, Drosophila melanogaster, including α-synuclein-induced degeneration of dopaminergic neurons, or dopamine (DA) loss by genetic elimination of neural DA synthesis. Defective behaviors in this latter model can be ameliorated by feeding the DA precursor L-DOPA, analogous to the treatment paradigm for PD. Secondary complication from L-DOPA treatment in PD patients are associated with ectopic synthesis of DA in serotonin (5-HT)-releasing neurons, leading to DA/5-HT imbalance. Here we examined the neuro-anatomical adaptations resulting from imbalanced DA/5-HT signaling in Drosophila mutants lacking neural DA. We find that, similar to rodent models of PD, lack of DA leads to increased 5-HT levels and arborizations in specific brain regions. Conversely, increased DA levels by L-DOPA feeding leads to reduced connectivity of 5-HT neurons to their target neurons in the mushroom body (MB). The observed alterations of 5-HT neuron plasticity indicate that loss of DA signaling is not solely responsible for the behavioral disorders observed in Drosophila models of PD, but rather a combination of the latter with alterations of 5-HT circuitry.
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影响因子：
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