| 1 | 生物。精神病学2005年6月57日：1493-503 |
|---|---|
| PMID | 15953485 |
| 标题 | 精神分裂症和D丝氨酸水平中SRR和DAO的多种丝氨酸种族友（SRR）mRNA同工型和遗传分析的鉴定。 |
| Abstract | 我们以前报道了D-serine的血清水平降低，D-丝氨酸是N-甲基-D-天冬氨酸（NMDA）受体的内源性共启动者schizophrenia，支持NMDA神经传递的低功能假设schizophrenia。在这项研究中，我们检查了丝氨酸种族酶的遗传作用（srr），一种从L丝氨酸催化D-丝氨酸的酶和D-氨基酸氧化酶（DAO）的敏感性schizophreniaand the regulation of serum D-serine levels. We determined the complete cDNA and genomic structures ofsrr并进行突变筛选。单核苷酸多态性（SNP）srr和Dao的关联测试schizophreniain both case-control and family-based designs and for correlation with serum levels of D-serine. Genomic analyses revealed that human brainsrr转录本由四种具有主要物种的同工型组成，这些同工型源自各种5'端外显子的替代使用。遗传关联分析显示srr/dao和schizophrenia。We replicated the decreased serum D-serine levels inschizophrenia在样本集中，但D丝氨酸水平与srr/DAO基因型。 Thesrr/DAO不太可能是发展的主要遗传决定因素schizophrenia或控制血清D丝氨酸水平。 |
| SCZ关键字 | 精神分裂症，精神分裂症，精神分裂症患者 |
| 2 | Psychiatr. Genet. 2007 Apr 17: 125 |
| PMID | 17413455 |
| 标题 | No association between the serine racemase gene (SRR) and schizophrenia in a German case-control sample. |
| Abstract | -1 |
| SCZ关键字 | 精神分裂症，精神分裂症，精神分裂症患者 |
| 3 | 生物。Psychiatry 2007 May 61: 1200-3 |
| PMID | 17067558 |
| 标题 | A genetic variant of the serine racemase gene is associated with schizophrenia. |
| Abstract | 丝氨酸种族酶（srr) is a brain-enriched enzyme that converts L-serine to D-serine, which acts as an endogenous ligand of N-methyl D-aspartate (NMDA) receptors. Dysfunction ofsrrmay reduce the function of NMDA receptors and susceptibility toschizophrenia。 We genotyped three single-nucleotide polymorphisms (SNPs) of the 5' region of thesrrgene in 525 patients withschizophreniaand 524 healthy controls. Effects of SNPs on the promoter activity and on serum levels of total and D-serine were examined. We found a significant excess of the IVS1a+465C allele of thesrrgene inschizophrenia, especially in the paranoid subtype (p = .0028). A reporter assay showed that the IVS1a+465C allele had 60% lower promoter activity than did the IVS1a+465G allele. The IVS1a+465C allele of thesrrgene, which reduces expression of the gene, is a risk factor forschizophrenia，尤其是偏执型亚型。 |
| SCZ关键字 | 精神分裂症，精神分裂症，精神分裂症患者 |
| 4 | Hum. Mol. Genet. 2009 Sep 18: 3227-43 |
| PMID | 19483194 |
| 标题 | 丝氨酸种族酶与人类和小鼠模型中的精神分裂症易感性有关。 |
| Abstract | 异常的N-甲基-D-天冬氨酸受体（NMDAR）功能与病理生理有关schizophrenia。D丝氨酸是重要的NMDAR调节剂，并阐明了D链合成酶丝氨酸种族友的作用（srr) inschizophrenia，我们通过ENU诱导的突变确定并表征了小鼠，这完全丧失了srr活性和大幅度降低的D丝氨酸水平。突变小鼠表现出与schizophrenia, including impairments in prepulse inhibition, sociability and spatial discrimination. Behavioral deficits were exacerbated by an NMDAR antagonist and ameliorated by d-serine or the atypical antipsychotic clozapine. Expression profiling revealed that thesrr突变影响了几个与schizophreniaand cognitive ability. Transcript levels altered by thesrrmutation were also normalized by d-serine or clozapine treatment. Furthermore, analysis ofsrr人类中的遗传变异确定了与schizophrenia。这项研究表明异常srrfunction and diminished d-serine may contribute toschizophrenia发病。 |
| SCZ关键字 | 精神分裂症，精神分裂症，精神分裂症患者 |
| 5 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2009 Apr 33: 511-8 |
| PMID | 19223009 |
| 标题 | Association analysis of glycine- and serine-related genes in a Japanese population of patients with schizophrenia. |
| Abstract | 与谷氨酸相关的氨基酸甘氨酸和丝氨酸水平的差异schizophrenic据报道，根据临床过程，患者和正常受试者以及这些氨基酸的血浆浓度变化。已经假设甘氨酸和丝氨酸代谢可能会改变schizophrenia。In fact, some genes related to the metabolism of these amino acids have been suggested to be candidate genes forschizophrenia。Thus, we performed a genomic case-control analysis of amino acid metabolism-related genes in Japanese patients withschizophrenia。Case-control genetic association analysis of PHGDH, SHMT1,srr, and DAO was performed. In addition, the effect of the various genotypes resulting from these four genes on changes in plasma amino acid levels inschizophreniawas assessed. The genetic case-control analysis showed that no individual single-nucleotide polymorphism (SNP) in any of the four genes was associated withschizophrenia;只有两个（RS3918347-RS4964770，P = 0.0009）和三个（RS3825251-RS3918347-RS4964770，P = 0.002），基于DAO基因的单倍型分析与DAO基因分析有关schizophrenia即使在校正多次测试之后。所研究的基因型均与血浆甘氨酸以及L-和D丝氨酸水平的变化有关schizophrenic临床课程。DAO基因可能是易感性的基因座schizophrenia。 |
| SCZ关键字 | 精神分裂症，精神分裂症，精神分裂症患者 |
| 6 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2009 Apr 33: 511-8 |
| PMID | 19223009 |
| 标题 | Association analysis of glycine- and serine-related genes in a Japanese population of patients with schizophrenia. |
| Abstract | 与谷氨酸相关的氨基酸甘氨酸和丝氨酸水平的差异schizophrenic据报道，根据临床过程，患者和正常受试者以及这些氨基酸的血浆浓度变化。已经假设甘氨酸和丝氨酸代谢可能会改变schizophrenia。In fact, some genes related to the metabolism of these amino acids have been suggested to be candidate genes forschizophrenia。Thus, we performed a genomic case-control analysis of amino acid metabolism-related genes in Japanese patients withschizophrenia。Case-control genetic association analysis of PHGDH, SHMT1,srr, and DAO was performed. In addition, the effect of the various genotypes resulting from these four genes on changes in plasma amino acid levels inschizophreniawas assessed. The genetic case-control analysis showed that no individual single-nucleotide polymorphism (SNP) in any of the four genes was associated withschizophrenia;只有两个（RS3918347-RS4964770，P = 0.0009）和三个（RS3825251-RS3918347-RS4964770，P = 0.002），基于DAO基因的单倍型分析与DAO基因分析有关schizophrenia即使在校正多次测试之后。所研究的基因型均与血浆甘氨酸以及L-和D丝氨酸水平的变化有关schizophrenic临床课程。DAO基因可能是易感性的基因座schizophrenia。 |
| SCZ关键字 | 精神分裂症，精神分裂症，精神分裂症患者 |
| 7 | Nihon Shinkei Seishin Yakurigaku Zasshi 2010 11月30日：197-200 |
| PMID | 21226315 |
| 标题 | [分析小鼠菌株依赖性的预硫抑制指向小鼠和精神分裂症中SHMT1（SHMT1）的作用]。 |
| Abstract | Deficits in prepulse inhibition (PPI) are thought to be a biological trait of mental illnesses, includingschizophrenia。It is known that the N-methyl-D-aspartate type glutamate (NMDA) receptor function affects PPI integrity and D-serine and glycine are typical endogenous co-agonists for the receptor. In parallel, we re-visited our prior quantitative trait loci (QTL) analysis study that examined C57BL/6 (B6) mice with high PPI and C3H/He (C3) with low PPI, and noticed that the genes encoding enzymes responsible for the productions of D-serine (serine racemase:srr）和甘氨酸（丝氨酸羟基转移酶1：SHMT1）映射到染色体11 QTL。因此，我们着手检查两个小鼠菌株之间两个氨基酸的脑间隙液（ISF）水平是否不同，使用体内微透析。与C3小鼠相比，在B6小鼠中，从额叶皮层的透析液中恢复了D丝氨酸和甘氨酸，在PPI中的表现较高。接下来，我们分析了两个基因，srrand Shmt1. We then identified promoter polymorphisms in Shmt1 which elicit lower transcriptional activity in B6 compared to C3 mice. Human studies revealed higher expression levels of SHMT1 in the frontal cortex of postmortem brains fromschizophrenics compared to controls, but no changes insrr水平。此外，遗传分析检测到SHMT1和schizophrenia。这些结果表明SHMT1（SHMT1）是调节小鼠PPI的遗传成分之一，与schizophreniasusceptibility in humans. |
| SCZ关键字 | 精神分裂症，精神分裂症，精神分裂症患者 |
| 8 | 精神分裂。res。2010年7月120日：236-7 |
| PMID | 20385472 |
| 标题 | 精神分裂症中升高的Pick1 mRNA增加了自杀中的SRR mRNA。 |
| Abstract | -1 |
| SCZ关键字 | 精神分裂症，精神分裂症，精神分裂症患者 |
| 9 | Nihon Shinkei Seishin Yakurigaku Zasshi 2010 11月30日：197-200 |
| PMID | 21226315 |
| 标题 | [分析小鼠菌株依赖性的预硫抑制指向小鼠和精神分裂症中SHMT1（SHMT1）的作用]。 |
| Abstract | Deficits in prepulse inhibition (PPI) are thought to be a biological trait of mental illnesses, includingschizophrenia。It is known that the N-methyl-D-aspartate type glutamate (NMDA) receptor function affects PPI integrity and D-serine and glycine are typical endogenous co-agonists for the receptor. In parallel, we re-visited our prior quantitative trait loci (QTL) analysis study that examined C57BL/6 (B6) mice with high PPI and C3H/He (C3) with low PPI, and noticed that the genes encoding enzymes responsible for the productions of D-serine (serine racemase:srr）和甘氨酸（丝氨酸羟基转移酶1：SHMT1）映射到染色体11 QTL。因此，我们着手检查两个小鼠菌株之间两个氨基酸的脑间隙液（ISF）水平是否不同，使用体内微透析。与C3小鼠相比，在B6小鼠中，从额叶皮层的透析液中恢复了D丝氨酸和甘氨酸，在PPI中的表现较高。接下来，我们分析了两个基因，srrand Shmt1. We then identified promoter polymorphisms in Shmt1 which elicit lower transcriptional activity in B6 compared to C3 mice. Human studies revealed higher expression levels of SHMT1 in the frontal cortex of postmortem brains fromschizophrenics compared to controls, but no changes insrr水平。此外，遗传分析检测到SHMT1和schizophrenia。这些结果表明SHMT1（SHMT1）是调节小鼠PPI的遗传成分之一，与schizophreniasusceptibility in humans. |
| SCZ关键字 | 精神分裂症，精神分裂症，精神分裂症患者 |
| 10 | J. Neurochem. 2010 Dec 115: 1374-85 |
| PMID | 20977478 |
| 标题 | Analysis of strain-dependent prepulse inhibition points to a role for Shmt1 (SHMT1) in mice and in schizophrenia. |
| Abstract | Deficits in prepulse inhibition (PPI) are known in mental illnesses, includingschizophrenia。NMDA受体功能会影响PPI完整性，而D-丝氨酸和甘氨酸是受体的内源性共振。我们以前使用具有更好PPI性能的C57BL/6（B6）小鼠和PPI得分较低的C3H/HE（C3）的定量性状基因座分析，表明D链合成酶和酶的基因在Glycine和L-酶之间进行可逆转化酶丝氨酸（srr和SHMT1分别位于相同的PPI量化性状基因座峰。因此，我们着手确定哪种基因可能解释了PPI差异，以及该基因是否可能与schizophrenia。We first examined brain interstitial fluid levels of the two amino acids using microdialysis. Recovery of D-serine and glycine from the dialysate was higher in B6, compared to C3. Next, we analyzed expression levels and genetic polymorphisms of the two genes. There were promoter polymorphisms in Shmt1, which elicit lower transcriptional activity in B6 compared to C3 conforming to the results of brain expression levels, but no functional genetic variants insrr。最后，我们评估了两种基因的表达水平schizophrenia和与该疾病的遗传关联。SHMT1水平更高schizophrenicbrains compared to controls, but no changes insrr水平。我们检测到SHMT1和schizophrenia。这些结果表明SHMT1（SHMT1），但不是srr,可能是其中的一个基因组件再保险gulating PPI in mice and possibly relevant toschizophrenia。 |
| SCZ关键字 | 精神分裂症，精神分裂症，精神分裂症患者 |
| 11 | J. Neurochem. 2010 Dec 115: 1374-85 |
| PMID | 20977478 |
| 标题 | Analysis of strain-dependent prepulse inhibition points to a role for Shmt1 (SHMT1) in mice and in schizophrenia. |
| Abstract | Deficits in prepulse inhibition (PPI) are known in mental illnesses, includingschizophrenia。NMDA受体功能会影响PPI完整性，而D-丝氨酸和甘氨酸是受体的内源性共振。我们以前使用具有更好PPI性能的C57BL/6（B6）小鼠和PPI得分较低的C3H/HE（C3）的定量性状基因座分析，表明D链合成酶和酶的基因在Glycine和L-酶之间进行可逆转化酶丝氨酸（srr和SHMT1分别位于相同的PPI量化性状基因座峰。因此，我们着手确定哪种基因可能解释了PPI差异，以及该基因是否可能与schizophrenia。We first examined brain interstitial fluid levels of the two amino acids using microdialysis. Recovery of D-serine and glycine from the dialysate was higher in B6, compared to C3. Next, we analyzed expression levels and genetic polymorphisms of the two genes. There were promoter polymorphisms in Shmt1, which elicit lower transcriptional activity in B6 compared to C3 conforming to the results of brain expression levels, but no functional genetic variants insrr。最后，我们评估了两种基因的表达水平schizophrenia和与该疾病的遗传关联。SHMT1水平更高schizophrenicbrains compared to controls, but no changes insrr水平。我们检测到SHMT1和schizophrenia。这些结果表明SHMT1（SHMT1），但不是srr,可能是其中的一个基因组件再保险gulating PPI in mice and possibly relevant toschizophrenia。 |
| SCZ关键字 | 精神分裂症，精神分裂症，精神分裂症患者 |
| 12 | J. Neurosci. Res. 2010 Jun 88: 1829-40 |
| PMID | 20091774 |
| 标题 | C6神经胶质瘤细胞中的D链氨酸代谢：丙氨酸 - 丝氨酸甲苯甲氨酸转运蛋白（ASCT2）和丝氨酸种族友（SRR）的参与，但不参与D-D-氨基酸氧化酶（DAO）。 |
| Abstract | D丝氨酸是内源性N-甲基-D-天冬氨酸（NMDA）受体辅助因素。它是由丝氨酸种族酶从l serine合成的（srr），但其代谢的许多方面尚不清楚，尤其是在前脑，缺乏活性D-氨基酸氧化酶（DAO），这是主要的D-丝氨酸降解酶。候选机制包括srroperating in alpha,beta-eliminase mode (converting D-serine to pyruvate) and regulation by serine transport, in which the alanine-serine-cysteine transporter ASCT2 is implicated. Here we report studies in C6 glioma cells, which "simulate" the forebrain, in that the cells expresssrr和ASCT2，但缺乏DAO活动。我们测量了d-serine，asct2，srr, and DAO expression and DAO activity in two situations: after incubation of cells for 48 hr with serine isomers and after increased or decreasedsrrexpression by transfection and RNA interference, respectively. Incubation with serine enantiomers decreased [(3)H]D-serine uptake and ASCT2 mRNA and increasedsrr免疫反应性但没有改变DAO免疫反应性，而DAO活性仍然无法检测到。srroverexpression increased D-serine and pyruvate and decreased [(3)H]D-serine uptake and ASCT2 mRNA but did not affect DAO.srrknockdown did not alter any of the parameters. Our data suggest that D-serine transport mediated by ASCT2 contributes prominently to D-serine homeostasis when DAO activity is absent. The factors regulating D-serine are important for understanding normal NMDA receptor function and because D-serine, along with DAO andsrr，与schizophrenia。 |
| SCZ关键字 | 精神分裂症，精神分裂症，精神分裂症患者 |
| 13 | Neuropharmacology 2012 Mar 62: 1484-503 |
| PMID | 21295046 |
| 标题 | D链途径对精神分裂症的贡献。 |
| Abstract | The glutamate neurotransmitter system is one of the major candidate pathways for the pathophysiology ofschizophrenia, and increased understanding of the pharmacology, molecular biology and biochemistry of this system may lead to novel treatments. Glutamatergic hypofunction, particularly at the NMDA receptor, has been hypothesized to underlie many of the symptoms ofschizophrenia，包括精神病，阴性症状和认知障碍。这篇综述将重点介绍NMDA受体的共同激动剂D-Serine与谷氨酸相结合，才能完全激活该离子通道受体。涉及D-丝氨酸，NMDA受体和相关分子的证据，例如D-氨基酸氧化酶（DAO），G72和丝氨酸种族酶（srr），在病因或病理生理学中schizophreniais discussed, including knowledge gained from mouse models with altered D-serine pathway genes and from preliminary clinical trials with D-serine itself or compounds modulating the D-serine pathway. Abnormalities in D-serine availability may underlie glutamatergic dysfunction inschizophrenia，以及通过D-丝氨酸途径起作用的新疗法的发展可能会显着改善许多人的预后schizophreniapatients. |
| SCZ关键字 | 精神分裂症，精神分裂症，精神分裂症患者 |
| 14 | Transl Psychiatry 2012 -1 2: e113 |
| PMID | 22832957 |
| 标题 | Association between SNPs and gene expression in multiple regions of the human brain. |
| Abstract | 鉴定DNA变异（单核苷酸多态性（SNP））和脑组织中的基因表达之间的遗传CIS关联可能是找到有助于有助于精神疾病病因的功能相关途径的一种有希望的方法。在这项研究中，我们检查了额叶皮层，海马，颞皮层，丘脑和小脑在患有精神疾病和正常对照的受试者中的遗传变异与基因表达之间的关联。我们确定了各个大脑区域中648个转录本和6725个SNP之间的CIS关联。几个SNP显示出大脑区域特异性关联。在此处测试的所有大脑区域中，仅一个基因PDE4DIP的表达水平与SNP RS12124527相关。从我们的数据中，我们生成了脑顺式表达定量特质基因座（EQTL）基因的列表，我们将schizophrenia从中下载的候选基因schizophreniaForum (SZgene) database (http://www.szgene.org/). Of the SZgene candidate genes, we found that the expression levels of four genes, HTR2A, PLXNA2,srrand TCF4, were significantly associated with cis SNPs in at least one brain region tested. One gene,srr，也参与了我们发现与疾病状况相关的共表达模块。此外，该模块还参与了大量的顺式EQTL基因，表明对脑组织的EQTL分析可能会鉴定出更可靠的敏感性基因schizophreniathan case-control genetic association analyses. In an attempt to facilitate the identification of genetic variations that may underlie the etiology of major psychiatric disorders, we have integrated the brain eQTL results into a public and online database, Stanley Neuropathology Consortium Integrative Database (SNCID; http://sncid.stanleyresearch.org). |
| SCZ关键字 | 精神分裂症，精神分裂症，精神分裂症患者 |
| 15 | PLOS ONE 2013 -1 8：E62438 |
| PMID | 23630632 |
| 标题 | Neonatal disruption of serine racemase causes schizophrenia-like behavioral abnormalities in adulthood: clinical rescue by d-serine. |
| Abstract | D丝氨酸是N-甲基-D-天冬氨酸（NMDA）受体的内源性共振，由丝氨酸racemase从L丝氨酸合成（NMDA）受体（NMDA）受体（srr）。鉴于D-丝氨酸在神经发育和病理生理学中的作用schizophrenia, we examined whether neonatal disruption of D-serine synthesis bysrrinhibition could induce behavioral abnormalities relevant toschizophrenia, in later life. Neonatal mice (7-9 days) were injected with vehicle or phenazine methosulfate (Met-Phen: 3 mg/kg/day), ansrr抑制剂。行为评估，例如自发的运动，新颖的对象识别测试（NORT）和预硫磺抑制（PPI），在少年（5-6周大）和成人（10-12周）阶段进行。此外，我们测试了新生儿对pHen暴露后D丝氨酸对成年小鼠PPI缺陷的影响。最后，我们评估了D-Serine是否可以防止schizophrenia-like behavior in these mice. Neonatal Met-Phen treatment reduced D-serine levels in the brain, 24 hours after the final dose. Additionally, this treatment caused behavioral abnormalities relevant to prodromal symptoms in juveniles and toschizophrenia在成年人中。单剂量的D丝氨酸改善了成年小鼠的PPI缺陷。有趣的是，慢性给药D-赛氨酸（900 mg/kg/day从p35到p70）显着阻止了新生儿元元暴露后的PPI缺陷发作。 This study shows that disruption of D-serine synthesis during developmental stages leads to behavioral abnormalities relevant to prodromal symptoms andschizophrenia, in later life. Furthermore, early pharmacological intervention with D-serine may prevent the onset of psychosis in adult. |
| SCZ关键字 | 精神分裂症，精神分裂症，精神分裂症患者 |
| 16 | Mol. Psychiatry 2015 Dec 20: 1557-64 |
| PMID | 25666758 |
| 标题 | Genome-wide association study of NMDA receptor coagonists in human cerebrospinal fluid and plasma. |
| Abstract | n -甲基- d受体(NMDAR) coagonists glycine, D-serine and L-proline play crucial roles in NMDAR-dependent neurotransmission and are associated with a range of neuropsychiatric disorders. We conducted the first genome-wide association study of concentrations of these coagonists and their enantiomers in plasma and cerebrospinal fluid (CSF) of human subjects from the general population (N=414). Genetic variants at chromosome 22q11.2, located in and near PRODH (proline dehydrogenase), were associated with L-proline in plasma (?=0.29; P=6.38 � 10(-10)). The missense variant rs17279437 in the proline transporter SLC6A20 was associated with L-proline in CSF (?=0.28; P=9.68 � 10(-9)). Suggestive evidence of association was found for the D-serine plasma-CSF ratio at the D-amino-acid oxidase (DAO) gene (?=-0.28; P=9.08 � 10(-8)), whereas a variant insrr(that encodes serine racemase and is associated withschizophrenia）构成CSF中L丝氨酸与D丝氨酸比率最密切相关的基因座。所有这些基因在啮齿动物脑膜和脉络丛中高度表达，与CSF生理有关的解剖区域。它们编码的酶和转运蛋白可能是针对的，以进一步确定NMDAR辅助参与NMDAR门控的性质。此外，可以在临床人群中随访突出的遗传变异。schizophreniaand 22q11 deletion syndrome. Overall, this targeted metabolomics approach furthers the understanding of NMDAR coagonist concentration variability and sets the stage for non-targeted CSF metabolomics projects. |
| SCZ关键字 | 精神分裂症，精神分裂症，精神分裂症患者 |