Mechanisms of compensation for loss of brain dopamine

描述(申请人提供)：多巴胺(DA)是动物王国中一种重要的神经递质/神经调节剂。在人类中，DA系统的功能障碍会导致运动、认知和情感障碍。在遗传模型系统中可行的详细研究允许电路水平定义负责特定行为的通路，允许详细的时间/空间控制DA合成，并有可能发现与人类DA功能障碍疾病相关的新的神经机制。在这个提案中，我们研究了一种新的自发抑制多巴胺丢失表型的方法。我们将使用遗传和分子技术来识别和描述导致这种抑制的遗传因素。我们的模型与早期帕金森氏症特别相关，在帕金森氏症中，描述不佳的通路可以部分补偿DA水平的下降，从而延迟症状的出现。这项建议侧重于这种补偿的机制。

DESCRIPTION (provided by applicant): Dopamine (DA) is an important neurotransmitter/ neuromodulator throughout the animal kingdom. In humans, dysfunction of the DA system leads to motor, cognitive, and affective disorders. Detailed studies feasible in the genetic model system Drosophila melanogaster permit circuit level definition of pathways responsible for specific behaviors, allow for detailed temporal/spatial control of DA synthesis, and have the potential to uncover novel neural mechanisms relevant to human diseases of DA dysfunction. In this proposal, we study a novel and spontaneous suppression of a subset of dopamine-loss phenotypes. We will use genetic and molecular techniques to identify and characterize the genetic elements responsible for this suppression. Our model is particularly relevant to early stage Parkinson's disease, where a poorly described pathway can partially compensate for decreased DA levels, delaying appearance of symptoms. This proposal focuses on the mechanisms of this compensation.