A Study of Muscarinic Receptors in Brain Tissue Obtained Postmortem from Subjects with Schizophrenia

本提案中概述的研究将检查人类大脑某些区域的分子组成，并确定这些区域的成分是否在精神分裂症患者的组织中发生了改变。精神分裂症是一种严重的精神疾病，影响了大约1%的澳大利亚人口，本提案中描述的研究旨在帮助了解这种疾病的原因，或者帮助开发治疗这种疾病的新药。该提案中概述的研究目标是确定大脑中被称为毒蕈碱受体的特定分子是否有变化。毒蕈碱受体是大脑中一种叫做乙酰胆碱的化学物质与大脑中的神经细胞交流的一种方式。已知乙酰胆碱控制大脑的重要功能，如记忆、认知和学习，所有这些功能都被认为在精神分裂症中受到影响。重要的是，所有这些功能的控制都涉及毒蕈碱受体，因此，这些受体的变化很可能产生精神分裂症的一些症状。我们现在希望扩展我们早期的研究，这些研究表明精神分裂症患者大脑中的毒蕈碱受体可能会发生变化，以确定5种毒蕈碱受体中的哪一种在大脑的哪个区域受到疾病病理的影响。根据我们现有的数据，我们可以预测，这些研究将增加毒蕈碱受体在精神分裂症中发生改变的论点的重要性，并提供关于如何使用靶向这些受体的药物来治疗这种疾病的重要信息。

The research outlined in this proposal will examine the molecular make up of certain regions of the human brain and determine if components within those regions are altered in tissue from subjects with schizophrenia. Schizophrenia is a serious psychiatric illness that affects approximately 1% of the Australian population and the research described in this proposal seeks to help understand the cause of the illness and-or to assist in the development of new drugs with which to treat the illness. The goal of the research outlined in this proposal is to determine if there are changes in specific molecules in the brain, termed muscarinic receptors. The muscarinic receptors are one way that a chemical in the brain called acetylcholine can communicate with the nerve cells in the brain. Acetylcholine is known to control important functions of the brain such as in memory, cognition and learning, all of these functions are thought to be affected in schizophrenia. Importantly, the control of all these functions involve muscarinic receptors and therefore, changes in those receptors could well produce some of the symptoms of schizophrenia. We now wish to extend our early studies which suggest there may be changes in muscarinic receptors in the brain of subjects with schizophrenia to determine which of the 5 muscarinic receptors are affected in which region of the brain by the pathology of the illness. From our existing data, we would predict that these studies will add weight to the argument that muscarinic receptors are altered in schizophrenia and provide vital information as to how drugs that target these receptors may be used to treat the illness.