Muscarinic M1 receptor, cognition and schizophrenia

毒蕈碱 M1 受体、认知和精神分裂症

• 批准号: nhmrc : 350344
• 负责人: A/Pr Elizabeth Scarr
• 金额: $ 39.93万
• 依托单位: The University of Melbourne
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2005
• 资助国家: 澳大利亚
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/muscarinic-m1-receptor-cognition-schizophrenia/82237
• 关键词: Muscarinic; M1; receptor; cognition; schizophrenia

Schizophrenia is a serious psychiatric illness that affects approximately 1% of Australia's population. Whilst the prominent symptom of schizophrenia is psychosis, the majority of subjects with schizophrenia also show deficits in cognition. Unlike psychotic symptoms, deficits in cognition do not respond well to current antipsychotic drug treatment. We have been investigating the possible role for changes in a family of receptors, called muscarinic receptors, in the pathology of schizophrenia for almost a decade. Our research has shown that two members of the muscarinic receptor family, the M1 and M4 receptors, may be differentially decreased in different brain regions of subjects with schizophrenia. Recently, we have shown that in the dorsolateral prefrontal cortex, the muscarinic receptor that is decreased in schizophrenia is the M1 receptor. Since we made this discovery another group has shown that a mutation in the M1 receptor may be a cause of cognitive deficits in schizophrenia. We are now proposing a study using parallel streams of research on postmortem brain tissue and in living subjects with schizophrenia to determine the likelihood that decreases in M1 receptors in the cortex may be the cause of cognitive deficits in schizophrenia. This will involve confirming that mutations in the M1 receptor, measured using DNA from white blood cells, are associated with cognitive deficits in schizophrenia. At the same time we will determine if the same mutation is associated with low levels of M1 receptors in cortex obtained postmortem from subjects with schizophrenia. If both these are true this will give us a strong platform to suggest that low levels of cortical M1 receptors are associated with cognitive deficits in schizophrenia.

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。虽然精神分裂症的突出症状是精神错乱，但大多数精神分裂症患者还表现出认知缺陷。与精神病症状不同，认知缺陷对目前的抗精神病药物治疗反应不佳。近十年来，我们一直在研究一种叫做毒蕈碱受体的受体家族的变化在精神分裂症病理中的可能作用。我们的研究表明，毒蕈碱受体家族的两个成员，M1和M4受体，在精神分裂症患者的不同脑区可能会有不同的减少。最近，我们发现在背外侧前额皮质中，精神分裂症患者减少的毒蕈碱受体是M1受体。自从我们有了这个发现之后，另一个小组已经证明M1受体的突变可能是精神分裂症认知缺陷的一个原因。我们现在提议进行一项研究，对死后脑组织和活的精神分裂症患者进行平行研究，以确定大脑皮层M1受体减少可能是精神分裂症患者认知缺陷的原因。这将涉及确认M1受体的突变（使用来自白细胞的DNA测量）与精神分裂症的认知缺陷有关。同时，我们将确定同样的突变是否与从精神分裂症患者死后获得的皮质M1受体的低水平有关。如果这两者都是正确的，这将为我们提供一个强有力的平台，表明低水平的皮质M1受体与精神分裂症的认知缺陷有关。