A neurodevelopmental pharmacological approach to the molecular pathophysiology of schizophrenic symptoms

精神分裂症症状分子病理生理学的神经发育药理学方法

基本信息

批准号：
14207040
负责人：
NISHIKAWA Toru
金额：
$ 32.2万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

Schizophrenic symptoms typically occur after the adolescence and the ability of psychotogenic drugs to induce schizophrenia-like psychosis is also age-dependent. Moreover, the behavioral responses to schizophrenomimetic drugs in experimental animals as pharmacological models of schizophrenia apparently depend upon postnatal development. The late developing manifestation of schizophrenia and its models suggest that the molecular cascades impaired in schizophrenia could be affected by or responsive to schizophrenomimetics only after the adolescence in humans or the critical period in experimental animals when the specific cascades might maturate. To obtain insight into the molecules that are specifically related to schizophrenia based upon the developmental features, we investigated in the developing rats the effects of schizophrenomimetic drugs, methamphetamine (MAP : a DA agonist which causes the schizophrenia-like positive symptoms) and phencyclidine (PCP : a NMDA antagonist causing schizophrenia-like positive and negative symptoms), on gene expression in the brain using a differential cloning technique and RT-PCR. We further studied the pharmacological profiles and the human homologues of previously identified a developmentally-regulated and MAP-responsive (mrt1) or PCP-responsive (prt1) gene in the neocortex In addition, we isolated the novel candidates for schizophrenia-related genes, mrt3 and prt4 from the neocrtex.

精神分裂症症状通常发生在青春期之后，并且精神生成药物诱导精神分裂症样精神病的能力也依赖于年龄。此外，作为精神分裂症的药理学模型，对精神分裂药物的行为反应显然取决于产后发育。精神分裂症及其模型的晚期发展表明，精神分裂症中所损害的分子级联反应只有在人类青春期或实验动物的关键时期或特定级联反应时，才能受到精神分裂症的影响或对精神分裂症的影响。 To obtain insight into the molecules that are specifically related to schizophrenia based upon the developmental features, we investigated in the developing rats the effects of schizophrenomimetic drugs, methamphetamine (MAP : a DA agonist which causes the schizophrenia-like positive symptoms) and phencyclidine (PCP : a NMDA antagonist causing schizophrenia-like positive and negative symptoms), on gene expression in the使用差分克隆技术和RT-PCR的大脑。我们还进一步研究了新皮层中先前鉴定出的发育调节和地图响应性（MRT1）或PCP响应性（PRT1）基因的药理学特征和人类同源物，此外，我们除了从Neocrtex中隔离了与Neocrtex的Schizophrenia相关基因，MRT3和PRT4的新型候选者。