Dopaminergic regulation by D-aminoacid oxidase, an enzyme implicated in schizophrenia

谷氨酸和多巴胺是大脑中的化学物质（神经递质），与严重的精神疾病精神分裂症密切相关。调节大脑中谷氨酸信号的分子之一是d -氨基酸氧化酶（DAO）。它通过分解另一种分子d -丝氨酸来做到这一点，d -丝氨酸是谷氨酸信号正常工作所必需的。我们的实验室和其他人最近的发现表明，DAO和d -丝氨酸在精神分裂症中受到影响。特别是，在患有这种疾病的人的大脑中，有太多的DAO，它太活跃了。这就产生了一种理论，即过量的DAO和不足的D-serine可能是？谷氨酸问题?在精神分裂症中，可能会导致精神分裂症患者的一些主要症状和困难。这个项目将研究一个具体的问题，即DAO在大脑中起什么作用，以及为什么它与精神分裂症有关。如上所述，多巴胺和谷氨酸都与精神分裂症有关，但我们对这两种神经递质之间的关系知之甚少。我们最近意外地发现，DAO存在于大脑中制造多巴胺的区域，这表明DAO可能提供了其中一个联系。因此，我们想研究降低DAO活性对大脑中多巴胺功能的影响，使用我们可以获得的一种新药。我们还将准确地绘制出DAO与多巴胺神经细胞的关系，以帮助解释它是如何以及在哪里工作的。这个项目建立在我们最近的发现和目前的专业知识的基础上，考虑到DAO对精神分裂症的病因和治疗的兴趣，它是及时和重要的。

Glutamate and dopamine are the brain chemicals (?neurotransmitters?) most involved in the severe mental illness called schizophrenia. One of the molecules that regulates glutamate signalling in the brain is D-amino acid oxidase (DAO). It does this by breaking down another molecule, D-serine, that is needed for glutamate signalling to work properly. Recent findings from our lab and others show that DAO and D-serine are affected in schizophrenia. In particular, there is too much DAO, and it is too active, in the brains of people with the illness. This leads to the theory that excessive DAO, and not enough D-serine, may be part of the ?glutamate problem? in schizophrenia and may contribute to some of the key symptoms and difficulties which patients with the illness experience. This project will examine a specific question about what DAO does in the brain and why it is relevant to schizophrenia. As noted above, dopamine as well as glutamate is involved in schizophrenia, yet we know little of the relationship between the two neurotransmitters. We recently found that DAO is, unexpectedly, present in the area of the brain that makes dopamine, suggesting that DAO may provide one of the links. We therefore want to study the effect of decreasing DAO activity on the function of dopamine in the brain, using a novel drug available to us. We will also map exactly where DAO is in relation to the dopamine nerve cells to help explain how and where it works. This project build upon our recent findings and current expertise, and is timely and important given the interest in DAO in the cause and the treatment of schizophrenia.