| 1 | Neuroscience 2008 Jun 154: 701-9 |
|---|---|
| PMID | 18495356 |
| Title | 在怀孕期间通过母体免疫激活调节胎儿多巴胺能的初步证据。 |
| Abstract | Maternal infection during pregnancy is an environmental risk factor for the offspring to develop severe brain disorders, includingschizophreniaand autism. However, only little is known about the neurodevelopmental mechanisms underlying the association between prenatal exposure to infection and the emergence of brain and behavioral dysfunctions in later life. Using a mouse model of prenatal immune challenge by the viral mimic polyriboinosinic-polyribocytidilic acid (PolyI:C), we explored the acute effects of maternal immune activation during pregnancy on the development of the fetal dopaminergic system, a neurotransmitter system known to be affected inschizophreniaand related disorders. We found that maternal immunological stimulation in early/middle pregnancy increased the number of mesencephalic dopamine neurons in the fetal brain at middle/late and late gestation. This effect was paralleled by changes in fetal expression of several genes known to be involved in dopamine neuron development, including the inductive signals sonic hedgehog (Shh) and fibroblast growth factor 8 (Fgf8), as well as transcription factors Nurr1 andPITX3。These findings provide initial in vivo evidence for a modulation of fetal dopaminergic development by maternal immune activation during pregnancy. Additional investigations of the neurodevelopmental effects of prenatal immune challenge are thus clearly warranted in order to further validate whether abnormal dopaminergic development may be a critical neuropathological mechanism underlying the precipitation ofschizophrenia-like brain and behavioral dysfunctions emerging after in utero exposure to infection. |
| SCZ Keywords | schizophrenia |
| 2 | prog。神经心理药物。生物。精神病学2010年8月34日：1094-7 |
| PMID | 20570600 |
| Title | Preliminary evidence that polymorphisms in dopamine-related transcription factors LMX1A, LMX1B and PITX3 are associated with schizophrenia. |
| Abstract | The early development of dopaminergic pathways has been attributed importance for the aetiology ofschizophrenia。Several transcription factors are involved in the survival and maturation of dopamine neurons, including LMX1A, LMX1B andPITX3。The possibility that polymorphisms in these genes may influence the development and/or the maintenance of dopaminergic neurons prompted us to investigate if five single nucleotide polymorphisms (SNPs) previously linked to Parkinson's disease are associated with this disorder. Preliminary evidence that genetic variation in LMX1A (rs6668493, rs4657411), LMX1B (rs10987386) andPITX3（RS4919621）可能会增加发展的风险schizophrenia被呈现。 |
| SCZ Keywords | schizophrenia |
| 3 | Neuroscience 2010 Mar 166: 391-6 |
| PMID | 20026251 |
| Title | Pitx3-deficient aphakia mice display unique behavioral responses to psychostimulant and antipsychotic drugs. |
| Abstract | The dorsal (A9) and ventral striatum (A10) of the midbrain mediate many of the effects of psychoactive drugs that alter emotion, cognition, and motor activity within the contexts of therapy or abuse. Although transgenic and knockout technologies have enabled development of genetic models to dissect contributions of specific dopamine (DA) receptor subtypes to psychoactive drug effects, few models exist that can distinguish contributions of A9 versus A10 circuits.PITX3是富含DA神经元的转录因子。阿法基亚（AK）小鼠缺乏PITX3显示选择失去黑哒,而另外一些er DA pathways are relatively spared, and therefore could be a useful tool for investigating the role of this subclass of DA projections. We investigated the effects of stimulants amphetamine, apomorphine, and MK-801 and the antipsychotic drug haloperidol on behavior in ak mice. Whereas wild-type mice showed the characteristic locomotor hyperactivity in response to amphetamine (5 mg/kg) and apomorphine (4 mg/kg), these drugs caused a paradoxical suppression of locomotor hyperactivity in ak mice. MK-801 (0.2 mg/kg) induced hyperactivity was maintained in both wt and ak mice. Additionally, mutant but not wild-type mice were insensitive to the cataleptic effects of haloperidol (1 mg/kg). These studies indicate that the nigrostriatal DA circuit plays a critical role in maintaining normal responsiveness to psychotropic drugs that either stimulate or block DA neurotransmission. We propose that ak mice may represent a valuable genetic model not only to study Parkinson's disease, but also to dissect the pathophysiologic and pharmacotherapuetic mechanisms of other DA-mediated disorders such as attention-deficit hyperactivity disorder, drug abuse andschizophrenia。 |
| SCZ Keywords | schizophrenia |
| 4 | Biol Open 2012 Aug 1: 693-704 |
| PMID | 23213462 |
| Title | Genome wide expression profiling of the mesodiencephalic region identifies novel factors involved in early and late dopaminergic development. |
| Abstract | Meso-diencephalic dopaminergic (mdDA) neurons are critical for motor control and cognitive functioning and their loss or dysfunction is associated with disorders such as Parkinson's disease (PD),schizophrenia和成瘾。但是，关于MDDA神经元发展和维持的分子机制知之甚少。在这里，我们确定了参与MDDA神经元发展的基因的时空图，以进一步了解其分子编程。在不同的发育阶段比较了发育中腹膜发育室中脑中脑（VM）的全基因组基因表达谱，从而通过烟碱丙氨酸受体（CHRNA6和CHRNB3亚基）鉴定了神经元信号传导的新调节作用，并鉴定出新的转录因子（OC2）（OC2）3）参与MDDA神经元场的产生。我们在这里表明PITX3, in cooperation with Nurr1, is the critical component in the activation of the Chrna6 and Chrnb3 subunits in mdDA neurons. Furthermore, we provide evidence of two divergent regulatory pathways resulting in the expression of Chrna6 and Chrnb3 respectively. |
| SCZ Keywords | schizophrenia |
| 5 | PLoS ONE 2012 -1 7: e42641 |
| PMID | 22870339 |
| Title | Spatial and temporal lineage analysis of a Pitx3-driven Cre-recombinase knock-in mouse model. |
| Abstract | Development and function of mesodiencephalic dopaminergic (mdDA) neurons has received a lot of scientific interest since these neurons are critically involved in neurological diseases as Parkinson and psychiatric diseases asschizophrenia, depression and attention deficit hyperactivity disorder (ADHD). The understanding of the molecular processes that lead to normal development and function of mdDA neurons has provided insight in the pathology and provided critical information on new treatment paradigms. In order to be able to study specific genetic ablation in mdDA neurons a new tools was developed that drives Cre-recombinase under the control of thePITX3locus. ThePITX3gene is well known for its specific expression in mdDA neurons and is present at the onset of terminal differentiation. Analysis of newly generatedPITX3-Cre knock-in mice shows that Cre expression, measured through the activation of eYfp by removal of a "Stop" signal (LoxP-Stop-LoxP-eYfp reporter mouse), is present at the onset of terminal differentiation and mimics closely the nativePITX3表达域。总之，我们在这里提出了一种新的Cre-Driver小鼠模型，该模型用于MDDA神经元中有趣的基因的限制消融，以提高我们对基本分子编程的理解。 |
| SCZ Keywords | schizophrenia |
| 6 | J. Neurosci. 2012 Aug 32: 10841-53 |
| PMID | 22875919 |
| Title | Schizophrenia-like features in transgenic mice overexpressing human HO-1 in the astrocytic compartment. |
| Abstract | 表观遗传学作用以将各种压力源转化为已建立的疾病模式的关键分子的描述将有助于预防和调整疾病的疗法对许多神经系统疾病的出现。在本文中，我们证明了新型GFAP的星形胶质细胞中应激蛋白血红素氧酶-1（HO-1）的选择性过表达。HMOX1转基因小鼠会导致皮层氧化应激和线粒体损伤/自噬。神经元的reelin含量减少（男性）；Nurr1和PITX3针对miRN和服务员抑制As, 145 and 133b; increased tyrosine hydroxylase and ?-synuclein expression with downregulation of the targeting miR-7b of the latter; augmented dopamine and serotonin levels in basal ganglia; reduced D1 receptor binding in nucleus accumbens; axodendritic pathology and altered hippocampal cytoarchitectonics; impaired neurovascular coupling; attenuated prepulse inhibition (males); and hyperkinetic behavior. The GFAP.HMOX1 neurophenotype bears resemblances to humanschizophrenia以及其他神经发育条件，并将神经胶质性HO-1视为对单胺能回路发展的不利（内源性和环境）影响的主要（内源性和环境）影响。在生命周期的战略点上，神经胶质HO-1对有害刺激的反应可能为有效管理人类神经发育和神经退行性条件提供新的机会。 |
| SCZ Keywords | schizophrenia |
| 7 | 经验。眼睛。2015年11月1日：-1 |
| PMID | 26593886 |
| Title | 从无眼到神经疾病。 |
| Abstract | 与年龄相关的白内障经常与眼部晶状体的退化性变化有关，包括蛋白质的聚集 - 主要是晶体蛋白，以及其他蛋白质，包括淀粉样蛋白（A？），导致假设可以用作阿尔茨海默氏病的“生物标志物”。即使戴维·比贝（David Beebe）的最后一篇论文（bei et aexp。Eye。，印刷中）拒绝了这一假设，寻找眼疾病和神经系统疾病之间的共同点也是一个令人着迷的方面。在这篇综述中，我主要从发展的角度讨论眼睛和大脑之间的这种共同点。果蝇无眼基因与哺乳动物PAX6基因的功能同源性的发现标志着眼睛发育遗传学的第一个亮点 - 这一结果破坏了蝇和哺乳动物眼睛发育的不同进化途径的“教条”。第二个亮点是发现PAX6还参与了支持许多基因的多效性作用的前脑的发展。这些发现为研究开辟了一条新的途径，表明各种转录因子，但结构蛋白在眼睛和大脑发育beplay苹果手机能用吗中均涉及，以及相应组织的功能完整性的维持。在这篇综述中，最新发现总结了，表明其突变首先被确定为先天性或少年眼疾病的基因也参与再生过程和神经发生（PAX6），也参与了像帕金森（Parkinson）这样的神经退行性疾病（例如，PITX3）或神经系统疾病schizophrenia(e.g. Crybb1, Crybb2). |
| SCZ Keywords | schizophrenia |
| 8 | Genes Brain Behav. 2016 Jan 15: 62-73 |
| PMID | 26548362 |
| Title | Development and function of the midbrain dopamine system: what we know and what we need to. |
| Abstract | The past two decades have seen an explosion in our understanding of the origin and development of the midbrain dopamine system. Much of this work has been focused on the aspects of dopamine neuron development related to the onset of movement disorders such as Parkinson's disease, with the intent of hopefully delaying, preventing or fixing symptoms. While midbrain dopamine degeneration is a major focus for treatment and research, many other human disorders are impacted by abnormal dopamine, including drug addiction, autism andschizophrenia。了解多巴胺神经元个体发育以及多巴胺连接和电路的发展如何为我们提供对其他与多巴胺相关疾病的潜在重要研究途径的关键见解。beplay苹果手机能用吗这篇综述将简要概述整个中脑多巴胺神经元的发展，以及我们对与中脑多巴胺神经元发展有关的行为和疾病相关的含义的了解。我们打算将两个广泛的神经科学领域的知识结合在一起，无论是发展性和行为的知识，目的是促进神经科学分支之间的更大讨论，以服务从发展的角度解决复杂的认知问题，并确定我们未来知识的重要差距学习。 |
| SCZ Keywords | schizophrenia |