| 1 | J. Neurochem。2005年10月95日：513-25 |
|---|---|
| PMID | 16144542 |
| Title | The effects of antipsychotics on beta-catenin, glycogen synthase kinase-3 and dishevelled in the ventral midbrain of rats. |
| Abstract | Protein kinase B and glycogen synthase kinase-3 have been identified as susceptibility genes for精神分裂症在大脑中检测到蛋白质和mRNA水平的改变精神分裂症S验尸。最近，我们报道了氟哌啶醇，氯氮平和利培酮改变大鼠前额叶皮层和纹状体的糖原合酶激酶3和β-蛋白酶蛋白的表达和糖原合酶激酶-3磷酸化水平。在当前的研究中，β-catenin，腺瘤息肉大肠杆菌，WNT1使用蛋白质印迹检查，在腹中脑和海马中检查了衣服和糖原合酶3。此外，使用共聚焦和荧光显微镜检查了在黑质和腹侧对剖面区域中检查β-catenin和GSK-3。结果表明，重复的抗精神病药物会导致腹中脑和海马中的糖原合酶激酶3，β-catenin和DishEvell-3蛋白水平的糖原合酶激酶3和DISHEVELLED-3蛋白水平的显着升高。RACLOPRIDE在腹中脑中会导致类似的β-catenin和GSK-3变化，这表明D2多巴胺受体拮抗作用介导了抗精神病药剂后观察到的变化。相比之下，苯丙胺是一种能够诱导精神病发作的药物，对腹中脑中的β-catenin和GSK-3具有相反的作用。总体而言，结果表明，抗精神病药可能通过对与规范WNT途径相关的蛋白质的修改产生有益作用。 |
| SCZ Keywords | 精神分裂症, schizophrenics |
| 2 | J. Neurochem。2005年10月95日：513-25 |
| PMID | 16144542 |
| Title | The effects of antipsychotics on beta-catenin, glycogen synthase kinase-3 and dishevelled in the ventral midbrain of rats. |
| Abstract | Protein kinase B and glycogen synthase kinase-3 have been identified as susceptibility genes for精神分裂症在大脑中检测到蛋白质和mRNA水平的改变精神分裂症S验尸。最近，我们报道了氟哌啶醇，氯氮平和利培酮改变大鼠前额叶皮层和纹状体的糖原合酶激酶3和β-蛋白酶蛋白的表达和糖原合酶激酶-3磷酸化水平。在当前的研究中，β-catenin，腺瘤息肉大肠杆菌，WNT1使用蛋白质印迹检查，在腹中脑和海马中检查了衣服和糖原合酶3。此外，使用共聚焦和荧光显微镜检查了在黑质和腹侧对剖面区域中检查β-catenin和GSK-3。结果表明，重复的抗精神病药物会导致腹中脑和海马中的糖原合酶激酶3，β-catenin和DishEvell-3蛋白水平的糖原合酶激酶3和DISHEVELLED-3蛋白水平的显着升高。RACLOPRIDE在腹中脑中会导致类似的β-catenin和GSK-3变化，这表明D2多巴胺受体拮抗作用介导了抗精神病药剂后观察到的变化。相比之下，苯丙胺是一种能够诱导精神病发作的药物，对腹中脑中的β-catenin和GSK-3具有相反的作用。总体而言，结果表明，抗精神病药可能通过对与规范WNT途径相关的蛋白质的修改产生有益作用。 |
| SCZ Keywords | 精神分裂症, schizophrenics |
| 3 | 翻译精神病学2013 -1 3：E301 |
| PMID | 24002087 |
| Title | A rare WNT1 missense variant overrepresented in ASD leads to increased Wnt signal pathway activation. |
| Abstract | Wnt signaling, which encompasses multiple biochemical pathways that regulate neural development downstream of extracellular Wnt glycoprotein ligands, has been suggested to contribute to major psychiatric disorders including autism spectrum disorders (ASD). We used next-generation sequencing and Sequenom genotyping technologies to resequence 10 Wnt signaling pathway genes in 198 ASD patients and 240 matched controls. Results for single-nucleotide polymorphisms (SNPs) of interest were confirmed in a second set of 91 ASD and 144 control samples. We found a significantly increased burden of extremely rare missense variants predicted to be deleterious by PolyPhen-2, distributed across seven genes in the ASD sample (3.5% in ASD vs 0.8% in controls; Fisher's exact test, odds ratio (OR)=4.37, P=0.04). We also found a missense variant inWNT1（S88R）在ASD样品中代表过多（267 ASD中的8 a/t（次要等位基因频率（MAF）= 1.69％）与377个对照中的1 A/T（MAF = 0.13％）或= 13.0，Fisher的确切确切测试，p = 0.0048; OR = 8.2和p = 0.053在校正人口分层后）。功能分析表明WNT1-s88r比野生型更活跃WNT1在Wnt/？ - catenin信号通路的测定中。我们对分布在10个Wnt信号通路中的7个中分布在测试的10个Wnt信号通路中的7个ASD负担的较高负担的发现，以及在该功能变体处的功能变体WNT1与ASD相关的基因座，该途径功能障碍的支持有助于ASD敏感性。考虑到ASD中常见分子机制的最新发现，精神分裂症和情感障碍，这些基因座在其他精神病疾病中也值得审查。 |
| SCZ Keywords | 精神分裂症, schizophrenics |
| 4 | J. Neurochem。2013年1月124日：241-9 |
| PMID | 23134367 |
| Title | Psychiatric disorder-related abnormal behavior and habenulointerpeduncular pathway defects in Wnt1-cre and Wnt1-GAL4 double transgenic mice. |
| Abstract | The neural crest is a unique structure in vertebrates.WNT1-cre和WNT1-GAL4双重转基因小鼠(壳体)已被使用in a variety of studies concerning neural crest cell lineages in which the Cre/loxP or GAL4/UAS system was applied. Here, we show psychiatric disorder-related behavioral abnormalities and histologic alterations in a neural crest-derived brain region in dTg mice. The dTg mice exhibited increased locomotor activity, decreased social interaction, and impaired short-term spatial memory and nesting behavior. The choline acetyltransferase- and vesicular glutamate transporter 2-immunoreactive habenulointerpeduncular fiber tracts that project from the medial habenular nucleus of the epithalamus to the interpeduncular nucleus of the midbrain tegmentum appeared irregular in the dTg mice. Both the medial habenula nucleus and the interpeduncular nucleus were confirmed to be derived from the neural crest. The findings of this study suggest that neural crest-derived cells have pathogenic roles in the development of psychiatric disorders and that the dTg mouse could be a useful animal model for studying the pathophysiology of mental illness such as autism and精神分裂症。使用DTG小鼠作为CRE转基因的Deleter系列的科学家在可能的毒性方面应该谨慎，尤其是在进行行为分析的情况下。 |
| SCZ Keywords | 精神分裂症, schizophrenics |
| 5 | J Mol Cell Biol 2014 Feb 6: 34-41 |
| PMID | 24326514 |
| Title | Wnt1-regulated genetic networks in midbrain dopaminergic neuron development. |
| Abstract | 神经元合成神经递质多巴胺在哺乳动物大脑中发挥关键功能。多巴胺合成神经元最大，最重要的人群位于哺乳动物腹中脑（VM）中，控制并调节运动，认知，情感，动机和有益的行为。这些神经元的退化导致运动缺陷是帕金森氏病的特征，而它们的功能障碍涉及精神疾病的发病机理，包括精神分裂症和成瘾。由于这些疾病的病因学和治疗前景包括神经发育方面，因此实质性科学兴趣集中在解释控制这些神经元在胚胎发育过程中的产生和存活的机械途径。beplay苹果手机能用吗在过去的十年中的研究揭示了分泌的关键作用WNT1配体及其信号传导级联反应在哺乳动物VM中产生多巴胺合成神经元中。在这里，我们总结了最初和最新的发现，这些发现已经解散了几个WNT1- 在中期胚胎阶段，VM祖细胞对多巴胺能细胞命运的增殖和承诺所需的控制遗传网络，以及这些祖细胞在中期和胎儿阶段将这些祖细胞正确分化为有丝氨酸后多巴胺合成神经元的正确分化。 |
| SCZ Keywords | 精神分裂症, schizophrenics |