| 1 | 是。J. Med。基因。2001年12月105日：753-7 |
|---|---|
| PMID | 11803525 |
| 标题 | 人NR4A2基因的突变分析是精神分裂症患者中脑多巴胺能神经发生的必不可少的基因。 |
| Abstract | Recent studies have revealed that an orphan receptor gene of the steroid/thyroid hormone nuclear receptor superfamily, the Nurr1 gene, is essential for the neurogenesis and differentiation of dopaminergic neurons in the midbrain of mice. Transgenic mice lacking the Nurr1 gene soon die after birth and are devoid of dopaminergic neurons in the midbrain. Heterozygous mice survive postnatally without obvious locomotor deficits; however, they have increased vulnerability to dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In view of the importance of dopamine neurotransmission in brain function, we were interested to know if the human homologous gene of murine Nurr1, theNR4A2gene, may play a role in the pathogenesis ofschizophrenia。We systematically sequenced all the exons of the humanNR4A2基因在中国人群中搜索分子变体schizophrenic来自台湾的患者。鉴定了两个分子变体：内含子6中的G插入（指定的IVS6 + 17 [请参见文本] + 18INSG），以及未翻译的外显子1（指定的C.-469delg）中的G-删除。IVS6 + 17 [见文本] + 18INSG是多态性的。然而，进一步的案例控制研究并未揭示这种多态性的关联schizophrenia。C.-469delg是177名无关患者中发现的一种罕见变体schizophrenicpatients, but not in 130 nonpsychotic controls. The result suggests that the c.-469delG and possibly other variants of theNR4A2基因可能与涉及的复杂因素有关schizophrenia。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | 是。J. Med。基因。2001年12月105日：753-7 |
| PMID | 11803525 |
| 标题 | 人NR4A2基因的突变分析是精神分裂症患者中脑多巴胺能神经发生的必不可少的基因。 |
| Abstract | Recent studies have revealed that an orphan receptor gene of the steroid/thyroid hormone nuclear receptor superfamily, the Nurr1 gene, is essential for the neurogenesis and differentiation of dopaminergic neurons in the midbrain of mice. Transgenic mice lacking the Nurr1 gene soon die after birth and are devoid of dopaminergic neurons in the midbrain. Heterozygous mice survive postnatally without obvious locomotor deficits; however, they have increased vulnerability to dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In view of the importance of dopamine neurotransmission in brain function, we were interested to know if the human homologous gene of murine Nurr1, theNR4A2gene, may play a role in the pathogenesis ofschizophrenia。We systematically sequenced all the exons of the humanNR4A2基因在中国人群中搜索分子变体schizophrenic来自台湾的患者。鉴定了两个分子变体：内含子6中的G插入（指定的IVS6 + 17 [请参见文本] + 18INSG），以及未翻译的外显子1（指定的C.-469delg）中的G-删除。IVS6 + 17 [见文本] + 18INSG是多态性的。然而，进一步的案例控制研究并未揭示这种多态性的关联schizophrenia。C.-469delg是177名无关患者中发现的一种罕见变体schizophrenicpatients, but not in 130 nonpsychotic controls. The result suggests that the c.-469delG and possibly other variants of theNR4A2基因可能与涉及的复杂因素有关schizophrenia。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | 是。J. Med。基因。2002年1月114日：15-23 |
| PMID | 11840500 |
| 标题 | Mutation analysis of the retinoid X receptor beta, nuclear-related receptor 1, and peroxisome proliferator-activated receptor alpha genes in schizophrenia and alcohol dependence: possible haplotype association of nuclear-related receptor 1 gene to alcohol dependence. |
| Abstract | Because retinoid cascades are involved in the regulation and development of the central nervous system, including dopaminergic neurons, retinoic acid signaling defects may contribute toschizophreniaand substances dependence. Retinoid X receptors (RXRs) form heterodimer complexes with nuclear-related receptor 1 (NURR1) or with peroxisome proliferator-activated receptors (PPARs). We examined 48 Japanese patients withschizophreniaand 32 patients with alcohol dependence to detect mutations in the retinoid X receptor beta gene (RXRB) on chromosome 6p21.3, the NURR1 gene (NR4A2) on chromosome 2q22-q23, and the PPAR alpha gene (PPARA) on chromosome 22q12.2-13.1. A Val95Ala polymorphism of the RXRB gene, a Val227Ala polymorphism in the PPARA gene, and two synonymous single-nucleotide and CA repeat polymorphisms in the 5' region and 3' untranslated region of theNR4A2鉴定了基因。扩展的病例对照样本并未表明疾病与RXRB或PPARA多态性之间的关联。但是，他们揭示了NR4A2基因单倍型和酒精依赖性，表明2q22-Q23包括NR4A2基因基因座是可能导致遗传易感性依赖性的基因组区域。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | 是。J. Med。基因。B Neuropsychiatr。基因。2003 Apr 118B: 20-4 |
| PMID | 12627459 |
| 标题 | Distribution of haplotypes derived from three common variants of the NR4A2 gene in Japanese patients with schizophrenia. |
| Abstract | Dysregulation in dopaminergic neurotransmission might play a role in the pathogenesis ofschizophrenia, and therefore genetic components of the dopamine (DA) pathway may confer risk. TheNR4A2(Nurr1) gene is essential for the development and maintenance of mesencephalic DA-synthesizing neurons. Moreover, Nurr1 forms a heterodimer with the retinoid X receptor and disturbances in the retinoid-signaling cascade may be involved in susceptibility toschizophrenia。研究的潜在遗传贡献NR4A2，我们使用基因[-2922（c）2-3，ivs6 + 17大约 + 18INSG，EX8 + 657（CA）9-10]中的三种常见变体进行了病例对照关联研究，这些变体与强烈的链接不平衡，与EX8 + 657（CA）9-10]进行了强烈的链接不平衡。彼此。我们没有检测到显着的等位基因或基因型关联。来自所有三种多态性的单倍型产生了相似的结果。这些数据不支持这样的观念NR4A2gene plays a major role in risk forschizophrenia在日本人中。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | 是。J. Med。基因。B Neuropsychiatr。基因。2003年7月120B：51-7 |
| PMID | 12815740 |
| 标题 | NURR1 promoter polymorphisms: Parkinson's disease, schizophrenia, and personality traits. |
| Abstract | 我们以前已经在Nurr1中的第三外显子中鉴定了突变（NR4A2) in two patients withschizophrenia(SZ) and one patient with bipolar disease with psychotic symptoms. In the present study we analyzed the promoter region of NURR1 and identified five polymorphic sites: three were found to be in strong linkage disequilibrium with a previously identified polymorphic site in the sixth intron. One polymorphism of this haplotype and the two other independent polymorphisms were investigated for their possible association with SZ and Parkinson's disease (PD) by comparing their frequencies in a Swedish material consisting of 134 subjects with SZ and 207 matched controls and 108 subjects with PD and 125 matched controls. Exon 1 was also investigated in our Parkinson and control material but no variances were found. The distributions of the two most informative polymorphisms in the promoter were investigated in an American material as well consisting of 141 subjects with SZ and 139 matched controls. Furthermore, the identified markers were screened for association with putative endophenotypes of SZ in the Swedish material. The distribution of sequence variants among the Swedish controls matched for SZ was investigated with regard to personality. No significant genotype or allelic association of the three sequence variants with SZ or PD was found. Several comparisons regarding endophenotypes or personality indicated association at the 5% confidence level, although correction for multiple testing rendered none of these findings significant. We conclude that the identified polymorphic sites in the human NURR1 are unlikely to be involved in conferring susceptibility for SZ or PD in our patient material. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | 是。J. Med。基因。B Neuropsychiatr。基因。2004年7月128B：41-5 |
| PMID | 15211629 |
| 标题 | NR4A2 and schizophrenia: lack of association in a Portuguese/Brazilian study. |
| Abstract | The present study investigates the association of mutations in the nuclear receptorNR4A2在schizophrenic患者。与人类NUR相关的受体1，NR4A2, is an orphan nuclear receptor that can be constitutively active as a transcription factor and for which no natural ligand has yet been identified. Alone or with retinoid X receptor, RXR,NR4A2影响破碎的几个基因的表达nt for human brain development and regulation. In the absence of Nurr1 (the mouse homologue to humanNR4A2），腹脑脑多巴胺能小鼠神经元证明了严重的发育衰竭，这种疾病在出生后不久是致命的。NURR1参与多巴胺能系统使其成为研究神经精神疾病的良好候选者，例如schizophreniaand Parkinson disease. Evidence by others support this hypothesis (1) mapping of theNR4A2基因至染色体2q22-23，该区域具有暗示性与schizophreniaand (2) identification of mutations in patients withschizophrenia（C.366-369deltac，c.308a> g，c.-469delg），躁狂抑郁症（c.289a> g）和家族性帕金森氏病（C.-291delt，c.-245t> g）。为了进一步扩展这些观察结果，我们在176个白种葡萄牙和82名白种人巴西受试者中搜索了所有这些突变schizophrenia。The study failed to identify any of the described mutations in patients or controls. Nevertheless, these negative results do not exclude altered expression of nuclear receptors inschizophreniaor the presence of other mutations. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | 是。J. Med。基因。B Neuropsychiatr。基因。2004年7月128B：41-5 |
| PMID | 15211629 |
| 标题 | NR4A2 and schizophrenia: lack of association in a Portuguese/Brazilian study. |
| Abstract | The present study investigates the association of mutations in the nuclear receptorNR4A2在schizophrenic患者。与人类NUR相关的受体1，NR4A2, is an orphan nuclear receptor that can be constitutively active as a transcription factor and for which no natural ligand has yet been identified. Alone or with retinoid X receptor, RXR,NR4A2影响破碎的几个基因的表达nt for human brain development and regulation. In the absence of Nurr1 (the mouse homologue to humanNR4A2），腹脑脑多巴胺能小鼠神经元证明了严重的发育衰竭，这种疾病在出生后不久是致命的。NURR1参与多巴胺能系统使其成为研究神经精神疾病的良好候选者，例如schizophreniaand Parkinson disease. Evidence by others support this hypothesis (1) mapping of theNR4A2基因至染色体2q22-23，该区域具有暗示性与schizophreniaand (2) identification of mutations in patients withschizophrenia（C.366-369deltac，c.308a> g，c.-469delg），躁狂抑郁症（c.289a> g）和家族性帕金森氏病（C.-291delt，c.-245t> g）。为了进一步扩展这些观察结果，我们在176个白种葡萄牙和82名白种人巴西受试者中搜索了所有这些突变schizophrenia。The study failed to identify any of the described mutations in patients or controls. Nevertheless, these negative results do not exclude altered expression of nuclear receptors inschizophreniaor the presence of other mutations. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 8 | 是。J. Med。基因。B Neuropsychiatr。基因。2005年2月133b：57-63 |
| PMID | 15635701 |
| 标题 | Identification and characterization of human NR4A2 polymorphisms in attention deficit hyperactivity disorder. |
| Abstract | 注意缺陷多动障碍（ADHD）是一种高度可遗传的和常见的障碍，部分原因是多巴胺功能的改变。NR4A2，或NURR1是一种孤儿核受体，与腹侧对接区域（VTA）和黑质Nigra（SN）的多巴胺能细胞的发展有关。VTA的多巴胺能细胞提供了对前额叶皮质的神经，据信在ADHD的病因中至关重要，这表明NR4A2是ADHD敏感性的潜在候选基因。这项研究旨在确定多态性NR4A2并测试他们与多动症的关联。数据库分析揭示了3'UTR中的CA重复多态性NR4A2这是PCR证实了。SSCP检测显示a common DeltaC polymorphism, 254 bp 5' to the transcriptional start site. These polymorphisms were tested for an association with ADHD in both a case control study of individuals from the Milwaukee Longitudinal Study of ADHD (103 cases and 66 controls), and in 35 families composed of trios or affected sib pairs (ASP) with ADHD. Functional effects of the promoter polymorphism were tested in vitro. The non-deleted allele was significantly more active in undifferentiated SK-N-MC cells compared to differentiated SK-N-MC and HeLa cells while a trend for increased activity for the DeltaC allele was observed in undifferentiated SK-N-MC cells. Identification of these polymorphisms may aid future candidate gene studies in disorders with altered dopamine signaling, such asschizophreniaParkinson's disease and ADHD. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 9 | Schizophr. Res. 2006 Jun 84: 253-71 |
| PMID | 16632332 |
| 标题 | Gene regulation by hypoxia and the neurodevelopmental origin of schizophrenia. |
| Abstract | Neurodevelopmental changes may underlie the brain dysfunction seen inschizophrenia。尽管在我们对遗传学的理解中取得了进步schizophrenia，关于非遗传因素如何与基因相互作用的知之甚少schizophrenia。目前对可能与之相关的基因的分析schizophrenia基于这样的观察结果，即缺氧在胚胎和胎儿脑中占上风，并且神经元基因之间的相互作用，缺氧的分子调节剂，例如缺氧诱导因子1（HIF-1）（HIF-1）和内在的缺氧在发育中的大脑中发生，并且可能可能发生。创建神经发育复杂变化的条件。因此，我们在文献中搜索了当前假设的候选基因的文献，以使其易感性schizophreniathat may be subject to ischemia-hypoxia regulation and/or associated with vascular expression. Genes were considered when at least two independent reports of a significant association withschizophrenia出现在文献中。分析表明，这些基因中有50％以上，尤其是AKT1，BDNF，CAPON，CCKAR，CHRNA7，CNR1，CNR1，COMT，DNTBP1，GAD1，GAD1，GRM3，IL10，MLC1，NOTCH4，NOTCH4，NRG1，NRG1，NRG1，NRG1，，NR4A2/nurr1，prodh，reln，rgs4，rtn4/nogo和TNF受到缺氧的调节和/或在脉管系统中表达。未来对提出的基因作为候选者的易感性的研究schizophreniashould include their possible regulation by physiological or pathological hypoxia during development as well as their potential role in cerebral vascular function. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 10 | J. Cell。生理学。2006年4月207日：49-57 |
| PMID | 16252282 |
| 标题 | 人神经祖细胞中酪氨酸羟化酶基因的调节不像鼠和大鼠系统中的Nurr1一样依赖于Nurr1。 |
| Abstract | 先前的研究人类的酪氨酸羟化酶(TH) promoter revealed remarkable differences in the mechanism of TH gene regulation between the human and murine models. Indeed, a low degree of homology was observed in the sequence of TH promoters among human, mouse, and rat systems. Only five short conserved regions (CRs) could be identified among the three species. A human TH minimal promoter was engineered and assembled into a self-inactivating lentiviral vector system. This human TH minimal promoter contained the five CRs plus the first -194 bp from the transcription start of the human TH promoter and the first 35 bp of the untranslated messenger RNA leader of the human TH gene. A significant degree of specificity for this human TH minimal promoter was observed only for human neuronal progenitor cells (hNPCs), but not for TH-positive differentiated mouse primary striatal and substantia nigra cells, indicating a significant difference in TH gene regulation between the human and mouse systems. Not only is the degree of homology between the human and mouse promoters in the range of only 46%, but also those few elements that share a high degree of homology display totally different functions in human and mouse brain-derived cells. In the rodent system,NR4A2（NURR1）是对最小启动子进行反式激活所必需的。有趣的是，Nurr1的二聚体和异二聚体结合位点都不存在于包含人类TH启动子的13 kb DNA序列中。取而代之的是，CRS称为人类的一个和四个启动子中的一个和四个启动子仅针对Nurr1的半腔结合位点序列编码，该序列未能在体外电泳迁移率分析（EMSA）中结合Nurr1。此外，在人类TH启动子中存在的三个单体NGFI-B响应元件（NBRE）核心位点（AggTCA）和两个与NBRE相关的位点，只有一个核心和两个NBRE相关位点形成蛋白质结合复合物。有趣的是，诱导时蛋白结合复合物的形成没有增加，在任何情况下都不会从复合物中supershift nurr1。这些发现共同证明了Nurr1的NBRE相关结合位点在介导Nurr1与人类TH启动子之间的相互作用中没有直接作用。同样，免疫组织化学和蛋白质印迹分析也证实，与小鼠模型相反，内源性NURR1表达均与HNPC中的TH基因表达呈正相关。此外，实时PCR分析表明，通过沉默的RNA分子介导的人Nurr1基因表达的下调不会影响分化HNPC中的人类基因表达。更好地了解人类基因调节可能对新型治疗方法的发展以及对各种神经系统疾病的发病机理的研究都具有重要意义，包括帕金森氏病，双相情感障碍和schizophrenia。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 11 | 摩尔。精神病学2007年8月12日：756-66 |
| PMID | 17457314 |
| 标题 | Adult mice with reduced Nurr1 expression: an animal model for schizophrenia. |
| Abstract | 转录因子nurr1（NR4A2）发现在中脑多巴胺能神经元的发展中起着至关重要的作用。Nurr1杂合（+/-）雄性和雌性小鼠在与正常水平的NurR1水平的35-40％的雄性和雌性小鼠中产生并在与与症状有关的动物模型中检查并检查schizophrenia。The Nurr1 (+/-) mice displayed hyperactivity in a novel environment, which persisted after administration of the dopamine-mimetic amphetamine and the N-methyl-D-aspartate receptor antagonist phencyclidine. The Nurr1 (+/-) mice were deficient in the retention of emotional memory and showed an enhanced response to swim stress. In addition, Nurr1 (+/-) male mice displayed a reduced dopamine turnover in the striatum and an enhanced dopamine turnover in the prefrontal cortex, while female mice showed an opposite pattern. These results show that Nurr1 (+/-) mice display a pattern of behaviors indicative of potential relevance for symptoms ofschizophrenia分别与纹状体和前额叶皮层中的性别特异性异常多巴胺传播结合在一起。这表明Nurr1突变小鼠可能是研究某些行为和分子机制的潜在动物模型schizophrenia。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 12 | 基因脑行为。2010年11月9日：910-7 |
| PMID | 20659174 |
| 标题 | Replicated association of the NR4A3 gene with smoking behaviour in schizophrenia and in bipolar disorder. |
| Abstract | schizophreniaand bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124),NR4A2（RS12803，RS834835）和NR4A3（RS1131339，RS1405209），在204个无关的样品中吸烟程度schizophrenia患者，其中包括126名吸烟者和78名非吸烟者。NR4A3基因中的SNP（RS1131339和RS1405209）与该队列中的大量吸烟显着相关，使用逐步分析每天吸烟的卷烟数量升级（p = 0.008和0.006）（分别满足NYHOLT的0.009，满足0.009，满意；多次测试的调整）。然后，我们在较大的319例躁郁症患者中重复了NR4A3标记（RS1131339和RS1405209）的关联分析，其中包括167名吸烟者和152名非吸烟者。我们已经复制了该组中NR4A3 SNP RS1131339的吸烟（p = 0.04）的正相关联（P = 0.04），这为NR4A3基因在尼古丁成瘾中的参与提供了重要的确认，这是一种精神疾病患者的尼古丁成瘾，这是一种尼古丁疾病的人群。瘾。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 13 | 翻译精神病学2011 -1 1：E9 |
| PMID | 22832404 |
| 标题 | 焦虑症的收敛功能基因组学：基因，生物标志物，途径和机制的转化鉴定。 |
| Abstract | 与其他主要的精神疾病（如双相情感障碍）和其他主要的精神疾病相比schizophrenia。它们更普遍，多样化和被认为是正常生活中的事实，可以解释这一相对的监督。此外，至于其他精神疾病，与候选基因和周围生物标志物的识别和验证有关的技术挑战。由于遗传异质性，可变环境暴露对基因表达的影响以及大型，表现良好的人群的困难，人类研究，尤其是遗传研究，易受能力不足的问题。动物模型基因表达研究在遗传均质和实验性触觉环境中可以避免伪影并提供检测的敏感性。随后将动物模型数据集与人类遗传和基因表达数据集的转化整合可以确保跨估计性的能力和疾病的特异性。我们已经使用了药物基因组学小鼠模型（涉及使用焦虑药物的治疗 - Yohimbine和抗焦虑药物 - 二氮伙这匹马）作为发现引擎，以鉴定焦虑候选基因以及潜在的血液生物标志物。使用收敛功能基因组学（CFG）方法分析了焦虑症（前额叶皮层，杏仁核和海马）和血液的基因表达变化，该方法将我们的新数据与已发表的人类和动物模型数据集成在一起，作为交叉的转换策略- 匹配和优先研究结果。我们的工作确定了顶级候选基因（例如FOS，GABBR1，NR4A2，drd1，adora2a，qki，rgs2，ptgd，hspa1b，dynll2，cckbr和dbp），脑血型生物标志物（例如FOS，QKI和HSPA1B），途径（例如CAMP信号）和焦虑症机制 - 涉及焦虑的机制对环境的转导和反应性，对海马有重要作用。总体而言，这项工作补充了我们以前的类似工作（关于双相情绪障碍和schizophrenia) conducted over the last decade. It concludes our programmatic first pass mapping of the genomic landscape of the triad of major psychiatric disorder domains using CFG, and permitted us to uncover the significant genetic overlap between anxiety and these other major psychiatric disorders, notably the under-appreciated overlap withschizophrenia。我们工作发现的PDE10A，TAC1和其他基因为经常观察到的临床合并症和焦虑与其他主要精神疾病之间的相互依赖性提供了分子基础，并将Schizo-Anxize焦虑视为可能的新病学领域。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 14 | Exp. Neurol. 2011 Nov 232: 22-32 |
| PMID | 21820432 |
| 标题 | Nurr1缺陷型小鼠中感觉运动门控缺陷与多巴胺能神经解剖学之间的关系。 |
| Abstract | Nurr1 (NR4A2）是一种孤儿核受体，对于多巴胺能神经元的发展和维持至关重要。NurR1的表达降低与帕金森氏病和其他多巴胺相关的疾病（例如schizophrenia。Nurr1的杂合本构缺失的小鼠中的最新实验工作表明，这种遗传操纵导致具有降低的惊悚症抑制声音反射的形式，导致感觉运动门控功能障碍。然而，这种行为表现的神经元物质基本未知。由于融合的证据支持中央多巴胺系统在调节预硫抑制中的关键作用，因此我们假设在成年Nurr1缺陷型小鼠中的预硫次抑制缺陷的出现可能与多巴胺能神经动物学变化有关。为了检验这一假设，我们遵循了一种受试者的方法，其中感官门控性能与相关纹状体和中脑区域中几种多巴胺能标记的验尸表达相关。我们发现，在NURR1缺陷型小鼠中的预硫抑制缺陷与表达酪氨酸羟化酶的底脂质多巴胺细胞的数量减少，并通过阳性肌腹膜肌室部分的酪氨酸羟化酶和多巴胺转运蛋白的免疫反应性降低。最有趣的是，我们还揭示了在背纹状体区域（凝岛壳）和腹侧纹状体区域的NURR1缺陷小鼠和腹侧纹状体区域的NurR1缺陷小鼠中的抑制水平与酪氨酸羟化酶免疫反应之间存在显着的负相关性。因此，我们的发现表明，Nurr1的杂合本构缺失引起的预硫次抑制缺陷的出现至少部分与纹状体多巴胺系统突触前成分的改变有关。在此观察到的NURR1缺陷小鼠中神经解剖学和行为改变的星座证实了先前的印象，即Nurr1下调的后果捕获了神经元和行为病理，尤其与帕金森氏病有关（但不限于）。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 15 | 大脑行为。免疫。2011年10月25日：1316-21 |
| PMID | 21723940 |
| 标题 | Nurr1 is not essential for the development of prepulse inhibition deficits induced by prenatal immune activation. |
| Abstract | 炎症引起的胎儿神经发育过程的破坏与长期行为异常和相关神经病理学的降水有关。在产前免疫激活模型中的最新纵向研究揭示了特定多巴胺能神经病理学的个体发育与多巴胺依赖性功能异常的不同形式的发作与涉及的不同形式的产后发作。schizophrenia。Two examples of such developmental correspondences are increased expression of the orphan nuclear receptor Nurr1 (NR4A2）在腹中间脑区域以及对声学惊吓反射的预硫化的破坏，仅在成人但不暴露于产前母体炎症的成年前受试者中出现神经解剖学和行为效应。在本研究中，我们检验了以下假设：NURR1可能是预硫化抑制缺陷的关键分子介质，由产前免疫激活诱导。为此，我们使用良好的母体免疫激活小鼠模型，通过暴露于野生型（WT）小鼠和小鼠中的成年PPI和小鼠的成年PPI的影响与杂合的本质删除。病毒模拟聚（I：c）（= polyriboinosinic-多利略西丁基酸）。我们发现，妊娠第9天的产前聚（I：C）治疗在破坏成人WT和Nurr1 +/-小鼠中的预硫抑制作用方面也有效。产前聚（I：C）处理通常还增加了中脑Nurr1阳性细胞，并抵消了黑质中遗传驱动的Nurr1缺陷。因此，我们的数据表明，至少在目前的实验条件下，Nurr1对于产前免疫激活引起的预硫次抑制缺陷并不是必不可少的。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 16 | 基因脑行为。2011年7月10日：589-603 |
| PMID | 21545404 |
| 标题 | Schizophrenia-relevant behaviors in a genetic mouse model of constitutive Nurr1 deficiency. |
| Abstract | Nurr1 (NR4A2) is an orphan nuclear receptor highly essential for the dopaminergic development and survival. Altered expression of Nurr1 has been suggested as a potential genetic risk factor for dopamine-related brain disorders, includingschizophrenia。为了支持这一点，在遗传修饰的小鼠中的最新实验工作表明，Nurr1的杂合本构缺失的小鼠表明了促进的发展schizophrenia-related behavioral abnormalities. However, the behavioral characterization of this Nurr1-deficient mouse model remains incomplete. This study therefore used a comprehensive behavioral test battery to evaluateschizophrenia- NURR1缺陷小鼠中的含量表型。我们发现，这些小鼠表现出增加的自发运动活性，并通过非竞争性的N-甲基-D-天冬氨酸（NMDA）受体拮抗剂Dizocilpine（MK-801）使用非竞争性的N-甲基-D-天冬氨酸（NMDA）受体拮抗剂（MK-801）进行运动治疗增强。此外，雄性但不是雌性Nurr1缺陷型小鼠在预硫次抑制和预硫化引起的反应性方面表现出明显的缺陷。但是，Nurr1缺失并未引起其他基本行为和认知功能的明显异常。schizophrenia，包括社会互动和认可，空间识别记忆或歧视逆转学习。因此，我们的发现表明，Nurr1的杂合本构删除导致受限的表型特征schizophrenia症状学主要与运动活动，感觉运动门控和对心理药物MK-801的反应性有关。这项研究进一步强调了多巴胺能发展在与人类精神病有关的特定脑功能障碍的沉淀中的关键作用。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 17 | Schizophr Bull 2013 5月39日：555-63 |
| PMID | 22294735 |
| 标题 | NR4A2: effects of an "orphan" receptor on sustained attention in a schizophrenic population. |
| Abstract | NR4A2(nuclear receptor subfamily 4 group A member 2) or Nurr1 is a transcription factor implied in the differentiation, maturation, and survival of dopaminergic neurons. It also has a role in the expression of several proteins that are necessary for the synthesis and regulation of dopamine (DA), such as tyrosine hidroxilase, dopamine transporter, vesicular monoamine transporter 2, and cRET. DA is an important neurotransmitter in attentional pathways. Our aim was to evaluate the influence ofNR4A2基因表现schizophrenia(SZ) patients and healthy subjects on a sustained attention task. For this study, we collected 188 SZ subjects (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and 100 control individuals. We genotyped 5 tag SNPs inNR4A2基因：RS1150143（C/G），RS1150144（A/G），RS834830（A/G），RS1466408（T/A）和RS707132（A/G）。我们还分析了其单倍型的影响（频率> 5％）。为了检查持续的关注，所有个体都完成了降解的刺激连续性能测试。我们评估了“命中”，“反应时间”，“敏感性A”和“错误警报”。在里面schizophrenic组，RS1150143，RS1150144，RS834830和RS707132的隐性基因型与性能较差有关。携带GGGTG单倍型的SZ受试者的命中率较小（p <.004），较低的感官A评分（p <.009）和较高的反应时间（p = .013）。我们观察到基因的性别效应：基因型和单倍型关联仅存在于男性组中。我们得出结论NR4A2基因参与SZ患者的注意缺陷，改变了命中，敏感性A和反应时间。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 18 | Schizophr Bull 2013 5月39日：555-63 |
| PMID | 22294735 |
| 标题 | NR4A2: effects of an "orphan" receptor on sustained attention in a schizophrenic population. |
| Abstract | NR4A2(nuclear receptor subfamily 4 group A member 2) or Nurr1 is a transcription factor implied in the differentiation, maturation, and survival of dopaminergic neurons. It also has a role in the expression of several proteins that are necessary for the synthesis and regulation of dopamine (DA), such as tyrosine hidroxilase, dopamine transporter, vesicular monoamine transporter 2, and cRET. DA is an important neurotransmitter in attentional pathways. Our aim was to evaluate the influence ofNR4A2基因表现schizophrenia(SZ) patients and healthy subjects on a sustained attention task. For this study, we collected 188 SZ subjects (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and 100 control individuals. We genotyped 5 tag SNPs inNR4A2基因：RS1150143（C/G），RS1150144（A/G），RS834830（A/G），RS1466408（T/A）和RS707132（A/G）。我们还分析了其单倍型的影响（频率> 5％）。为了检查持续的关注，所有个体都完成了降解的刺激连续性能测试。我们评估了“命中”，“反应时间”，“敏感性A”和“错误警报”。在里面schizophrenic组，RS1150143，RS1150144，RS834830和RS707132的隐性基因型与性能较差有关。携带GGGTG单倍型的SZ受试者的命中率较小（p <.004），较低的感官A评分（p <.009）和较高的反应时间（p = .013）。我们观察到基因的性别效应：基因型和单倍型关联仅存在于男性组中。我们得出结论NR4A2基因参与SZ患者的注意缺陷，改变了命中，敏感性A和反应时间。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 19 | 摩尔。精神病学2014年4月19日：478-85 |
| PMID | 23528911 |
| 标题 | 精神分裂症个体背外侧前额叶皮层中基因表达改变。 |
| Abstract | 的基本病理schizophrenia（SZ）可能与症状一样异质。包括前额叶皮层在内的各种皮质和皮质下区域已与其病理有关，并且已经将许多基因确定为疾病发展的危险因素。我们使用原位杂交（ISH）检查了从19个患者诊断为SZ和33个对照组的人，检查了背外侧前额叶皮层中58个基因的表达（DLPFC，由Brodmann地区9和46组成）。基于以下基因选择基因：（1）先前的识别作为SZ的危险因素；（2）细胞类型标记或（3）层流标记。比较了DLPFC中的细胞密度和染色强度，并在Brodmann区域9和46中分别进行了比较。与对照相比，SZ中的SZ中有多种基因的表达模式发生了变化。其他基因，包括C8orf79和NR4A2, showed alterations in cell density or staining intensity between the groups, highlighting the need for additional studies. Alterations were, with only a few exceptions, limited to Brodmann area 9, suggesting regional specificity of pathology in the DLPFC. Our results agree with previous studies on the GABAergic involvement in SZ, and suggest that areas 9 and 46 may be differentially affected in the disease. This study also highlights additional genes that may be altered in SZ, and indicates that these potentially interesting genes can be identified by ISH and high-throughput image analysis techniques. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 20 | J VIS EXP 2015 -1 -1：E52963 |
| PMID | 26325389 |
| 标题 | Production of Nurr-1 Specific Polyclonal Antibodies Free of Cross-reactivity Against Its Close Homologs, Nor1 and Nur77. |
| Abstract | 核受体亚家族4（NR4A）由3种相关蛋白组成，共享DNA结合结构域（DBD）和一个配体结合域（LBD）。核受体相关的1蛋白（Nurr1或NR4A2）在维持多巴胺能系统中起关键作用。与Nurr1基因相关的多巴胺功能障碍包括帕金森氏病，schizophreniaand manic depression among others. Furthermore, recent evidence indicates that Nurr1 is also expressed in other brain areas such as the hippocampus and plays critical roles for learning and memory. The other members of the family are nerve growth factor IB (Nur77 or NR4A1) and neuron-derived orphan receptor 1 (NOR1 or NR4A3). To help investigate the precise functional roles of Nurr1 in dopaminergic and other brain region-related neuronal dysfunctions antibodies devoid of cross-reactivities against Nur77 and NOR1 were needed. Since the proteins are more divergent in their LBDs than in their DNA binding domains immunization with purified LBDs should yield antibodies specific for Nurr1 with minimal reactivities against Nur77 and/or NOR1. Although anti-Nurr1 antibodies were successfully generated these showed significant immunoreactivity against the other members of the family. Affinity chromatography over immobilized Protein A followed by pre-adsorption against immobilized Nur77 and NOR1 LBDs yielded Nurr1 specific antibodies free of cross-reactivity. Here, we selectively target antibodies against a specific member of a highly conserved family of proteins by immunizing animals with their most divergent regions followed by removing cross reactive antibodies by pre-adsorption. The goal of the protocol is to increase polyclonal antibodies specificity through pre-adsorption against cross-reactive antigens. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 21 | Neurosci。Lett。2015年6月598：85-90 |
| PMID | 25982322 |
| 标题 | Association between NR4A2 genetic variation and schizophrenia: A comprehensive systematic review and meta-analysis. |
| Abstract | Homo Sapiens核受体亚家族4，A组（NR4A2）遗传变异已被认为是schizophrenia（SZ）。然而，结果尚无定论。我们进行了全面的系统审查和荟萃分析，以量化NR4A2SZ风险的变化。通过搜索PubMed Ovid，EBSCO，PSYCINFO和ISI知识网络搜索，所有合格的病例对照研究都迄今已发布到2014年9月。使用95％置信区间的合并优势比用于固定或随机效应模型中的关联强度。七项研究报告了17种具有3027名参与者的变体。在这些变体中，仅存在五个（rs143618355，rs199674295，c.366-369 del tac，c.-469delg和p4），而三个案件中出现，rs35479735（rs35479735，rs3832066和rs3832066 and rs397777066666666666674-）总体而言，在等位基因模型，主要模型和隐性模型下，这三个变体与SZ风险之间没有显着关联。结果未能揭示NR4A2多态性和SZ风险。但是，有必要进行大型且精心设计的研究以验证我们的发现。 |
| SCZ Keywords | schizophrenia, schizophrenic |