Indentification of mutations in excitatory amino acid receptor gene in schizophrenia

精神分裂症兴奋性氨基酸受体基因突变的鉴定

• 批准号: 11670944
• 负责人: SHIRAKAWA Osamu
• 金额: $ 2.24万
• 依托单位: Kobe University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670944/
• 关键词: schizophrenia; excitatory amino acid; NMDA receptor; polymorphism; mutation

N-methyl-D-aspartate (NMDA) receptor antagonists are known to produce a syndrome resembling schizophrenia, probably due to their blockade of NMDA receptors. The NMDA receptor 2B (NR2B) subunit has been identified as one of the major proteins in the postsynaptic density at glutamatergic synapses. Dysregulation of the NR2B subunit in the brain may be involved in the etiology of schizophrenia , consistent with the neurodevelopment hypothesis for the origin of this disorder. We screened for the genetic variation the NR2B subunit gene in patients with schizophrenia and studied the association between schizophrenia and a novel polymorphism of the NR2B subunit gene. One silent mutation (2664C/T) was identified in the region of NR2B subunit gene encoding the carboxyl-terminal intracellular domain. No significant differences in the frequencies of 2664C/T genotypes and alleles were found between patients with schizophrenia and healthy comparison subjects. Our findings provided no evidence association between schizophrenia and the 2664C/T polymorphism of the NR2B subunit.

N-甲基-D-天冬氨酸(NMDA)受体拮抗剂已知会产生一种类似精神分裂症的综合征，可能是由于它们阻断了NMDA受体。NMDA受体2B(NR2B)亚单位是谷氨酸能突触突触后密度的主要蛋白质之一。大脑中NR2B亚单位的失调可能与精神分裂症的病因有关，这与这种疾病的起源的神经发育假说是一致的。我们筛选了精神分裂症患者NR2B亚单位基因的遗传变异，并研究了NR2B亚单位基因的一种新的多态性与精神分裂症的相关性。在NR2B亚单位基因编码胞内羧基末端区域发现1个沉默突变(2664C/T)。精神分裂症患者2664C/T等位基因频率和等位基因频率与正常对照组比较差异无统计学意义。我们的发现没有证据表明精神分裂症与NR2B亚单位2664C/T多态有关。

项目成果

白川治 ほか.: "細胞内情報伝達系と精神分裂病."脳の科学. 21. 369-376 (1999)

Osamu Shirakawa 等人：“细胞内信号转导系统和精神分裂症。” 21. 369-376 (1999)

白川 治: "細胞内情報伝達系と精神分裂病"脳の科学. 21. 369-376 (1999)

Osamu Shirakawa：“细胞内信号转导系统和精神分裂症”《脑科学》21. 369-376 (1999)。

Maeda,K. et al: "Functional Serotonin Transporter Gene Polymorphism andSuicidality"Singapore Med J. 41(3). 23-24 (2000)

前田，K.

Maeda,K. et al: "Functional Serotonin Transporter Gene Polymorphism and Suicidality"Singapore Med J. 41(3). 23-24 (2000)

前田，K.

橋本健志 ほか: "精神分裂病死後脳におけるホスホリパーゼCの変化"精神薬療研究年報. 第32集. 85-93 (2000)

Kenji Hashimoto 等人：“精神分裂症死后大脑中磷脂酶 C 的变化”精神药理学治疗年度报告第 32 卷 85-93 (2000)