| 1 | Front Behav Neurosci 2008 -1 2：4 |
|---|---|
| PMID | 18958194 |
| 标题 | Mice lacking the kf-1 gene exhibit increased anxiety- but not despair-like behavior. |
| 抽象的 | KF-1最初认定为一种编码的蛋白质d by human gene with increased expression in the cerebral cortex of a patient with Alzheimer's disease. In mouse brain, kf-1 mRNA is detected predominantly in the hippocampus and cerebellum, and kf-1 gene expression is elevated also in the frontal cortex of rats after chronic antidepressant treatments. KF-1 mediates E2-dependent ubiquitination and may modulate cellular protein levels as an E3 ubiquitin ligase, though its target proteins are not yet identified. To elucidate the role of kf-1 in the central nervous system, we generated kf-1 knockout mice by gene targeting, using Cre-LOX重组。所得的KF-1（ - / - ）小鼠的外观正常且健康。行为分析表明，与光/黑暗过渡和升高的迷宫测试相比，KF-1（ - / - ）小鼠与KF-1（+/+）同窝仔相比，焦虑样行为显着增加。但是，使用开放式测试或使用强制游泳和尾悬架测试的行为绝望，在探索性运动中未观察到显着差异。这些观察结果表明，KF-1可能通过调节其未知靶标的蛋白质水平在生理条件下选择性抑制焦虑。有趣的是，KF-1（ - / - ）小鼠表现出明显增加的预硫抑制作用，通常在人类中降低精神分裂症patients. Thus, the kf-1(-/-) mice provide a novel animal model for elucidating molecular mechanisms of psychiatric diseases such as anxiety/depression, and may be useful for screening novel anxiolytic/antidepressant compounds. |
| SCZ Keywords | 精神分裂症, schizophrenic, schizophrenics |
| 2 | Front Behav Neurosci 2008 -1 2：4 |
| PMID | 18958194 |
| 标题 | Mice lacking the kf-1 gene exhibit increased anxiety- but not despair-like behavior. |
| 抽象的 | KF-1最初认定为一种编码的蛋白质d by human gene with increased expression in the cerebral cortex of a patient with Alzheimer's disease. In mouse brain, kf-1 mRNA is detected predominantly in the hippocampus and cerebellum, and kf-1 gene expression is elevated also in the frontal cortex of rats after chronic antidepressant treatments. KF-1 mediates E2-dependent ubiquitination and may modulate cellular protein levels as an E3 ubiquitin ligase, though its target proteins are not yet identified. To elucidate the role of kf-1 in the central nervous system, we generated kf-1 knockout mice by gene targeting, using Cre-LOX重组。所得的KF-1（ - / - ）小鼠的外观正常且健康。行为分析表明，与光/黑暗过渡和升高的迷宫测试相比，KF-1（ - / - ）小鼠与KF-1（+/+）同窝仔相比，焦虑样行为显着增加。但是，使用开放式测试或使用强制游泳和尾悬架测试的行为绝望，在探索性运动中未观察到显着差异。这些观察结果表明，KF-1可能通过调节其未知靶标的蛋白质水平在生理条件下选择性抑制焦虑。有趣的是，KF-1（ - / - ）小鼠表现出明显增加的预硫抑制作用，通常在人类中降低精神分裂症patients. Thus, the kf-1(-/-) mice provide a novel animal model for elucidating molecular mechanisms of psychiatric diseases such as anxiety/depression, and may be useful for screening novel anxiolytic/antidepressant compounds. |
| SCZ Keywords | 精神分裂症, schizophrenic, schizophrenics |
| 3 | Proc。纳特。学院科学。美国2009年3月106日：4507-12 |
| PMID | 19240213 |
| 标题 | Impaired maturation of dendritic spines without disorganization of cortical cell layers in mice lacking NRG1/ErbB signaling in the central nervous system. |
| 抽象的 | Neuregulin-1 (NRG1) and its ErbB2/B4 receptors are encoded by candidate susceptibility genes for精神分裂症但是，CNS中NRG1信号的基本功能仍不清楚。使用Cre/LOX技术，我们已经灭活了CNS中专门的ERBB2/B4介导的NRG1信号。与预期相反，大脑皮质，海马和小脑在突变小鼠中正常发育。取而代之的是，ERBB2/B4的丧失会损害树突状脊柱成熟和突触后支架蛋白与谷氨酸受体的相互作用。相反，升高的NRG1水平促进脊柱成熟。ERBB2/B4缺陷型小鼠表现出增加的攻击性和减少的预硫抑制作用。用抗精神病药治疗氯氮平可逆转行为和脊柱缺陷。我们得出的结论是，ERBB2/B4介导的NRG1信号传导调节了树突状脊柱成熟，并且谷氨酸能突触的缺陷可能有助于ERBB2/B4缺陷小鼠的行为异常。 |
| SCZ Keywords | 精神分裂症, schizophrenic, schizophrenics |
| 4 | Infect. Immun. 2014 Jul 82: 2670-9 |
| PMID | 24686056 |
| 标题 | 一个LOX12 in human toxoplasmosis. |
| 抽象的 | 一个LOX12 is a gene encoding arachidonate 12-lipoxygenase (12-LOX），非血红素脂氧酶家族的成员。一个LOX12 catalyzes the addition of oxygen to arachidonic acid, producing 12-hydroperoxyeicosatetraenoic acid (12-HPETE), which can be reduced to the eicosanoid 12-HETE (12-hydroxyeicosatetraenoic acid). 12-HETE acts in diverse cellular processes, including catecholamine synthesis, vasoconstriction, neuronal function, and inflammation. Consistent with effects on these fundamental mechanisms, allelic variants of ALOX12 are associated with diseases including精神分裂症, atherosclerosis, and cancers, but the mechanisms have not been defined. Toxoplasma gondii is an apicomplexan parasite that causes morbidity and mortality and stimulates an innate and adaptive immune inflammatory reaction. Recently, it has been shown that a gene region known as Toxo1 is critical for susceptibility or resistance to T. gondii infection in rats. An orthologous gene region with ALOX12 centromeric is also present in humans. Here we report that the human ALOX12 gene has susceptibility alleles for human congenital toxoplasmosis (rs6502997 [P, <0.000309], rs312462 [P, <0.028499], rs6502998 [P, <0.029794], and rs434473 [P, <0.038516]). A human monocytic cell line was genetically engineered using lentivirus RNA interference to knock down ALOX12.LOX12个敲低细胞，一个LOX12 RNA expression decreased and levels of the ALOX12底物，花生四烯酸增加。一个LOX12 knockdown attenuated the progression of T. gondii infection and resulted in greater parasite burdens but decreased consequent late cell death of the human monocytic cell line. These findings suggest that ALOX12 influences host responses to T. gondii infection in human cells. ALOX12 has been shown in other studies to be important in numerous diseases. Here we demonstrate the critical role ALOX12在人类的T. gondii感染中。 |
| SCZ Keywords | 精神分裂症, schizophrenic, schizophrenics |
| 5 | Prog. Lipid Res. 2014 Jan 53: 1-17 |
| PMID | 24334113 |
| 标题 | Long-chain polyunsaturated fatty acids (LCPUFA) from genesis to senescence: the influence of LCPUFA on neural development, aging, and neurodegeneration. |
| 抽象的 | Many clinical and animal studies demonstrate the importance of long-chain polyunsaturated fatty acids (LCPUFA) in neural development and neurodegeneration. This review will focus on involvement of LCPUFA from genesis to senescence. The LCPUFA docosahexaenoic acid and arachidonic acid are important components of neuronal membranes, while eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid also affect cardiovascular health and inflammation. In neural development, LCPUFA deficiency can lead to severe disorders like精神分裂症和注意力缺陷多动障碍。补充围产期LCPUFA对人类和啮齿动物的神经发育表现出有益的作用，从而改善了认知和感觉运动整合。在正常衰老中，将讨论LCPUFA对预防认知障碍的影响。LCPUFA对于神经元膜完整性和功能很重要，也有助于预防脑部灌注不足。脑灌注可能因肥胖，脑血管疾病，高血压或糖尿病类型2型损害。最后，我们将重点介绍LCPUFA在最常见的神经退行性疾病中的作用，例如阿尔茨海默氏病和帕金森氏病。这些疾病的特征是认知和连通性受损，临床和动物补充研究都表明LCPUFA的潜力减少了神经变性和炎症。这篇评论表明，LCPUFA在整个生命中都是必不可少的。 |
| SCZ Keywords | 精神分裂症, schizophrenic, schizophrenics |
| 6 | Neurobiol. Dis. 2015 Apr 76: 137-58 |
| PMID | 25684539 |
| 标题 | 有针对性的表达多巴胺受体细胞的有针对性消融的条件突变体中的运动和行为表型。 |
| 抽象的 | D1-dopamine receptors (Drd1a) are highly expressed in the deep layers of the cerebral cortex and the striatum. A number of human diseases such as Huntington disease and精神分裂症已知具有涉及多巴胺受体表达神经元的皮质病理学。为了阐明他们的功能角色，我们利用了Cre/LOXmolecular paradigm to generate Emx-1(tox) MUT mice, a transgenic line in which cortical Drd1a-expressing pyramidal neurons were selectively ablated. Emx-1(tox) MUT mice displayed prominent forelimb dystonia, hyperkinesia, ataxia on rotarod testing, heightened anxiety-like behavior, and age-dependent abnormalities in a test of social interaction. The latter occurred in the context of normal working memory on testing in the Y-maze and for novel object recognition. Some motor and behavioral abnormalities in Emx-1(tox) MUT mice overlapped with those in CamKII?(tox) MUT transgenic mice, a line in which both striatal and cortical Drd1a-expressing cells were ablated. Although Emx-1(tox) MUT mice had normal striatal anatomy, both Emx-1(tox) MUT and CamKII?(tox) MUT mice displayed selective neuronal loss in cortical layers V and VI. This study shows that loss of cortical Drd1a-expressing cells is sufficient to produce deficits in multiple motor and behavioral domains, independent of striatal mechanisms. Primary cortical changes in the D1 dopamine receptor compartment are therefore likely to model a number of core clinical features in disorders such as Huntington disease and精神分裂症. |
| SCZ Keywords | 精神分裂症, schizophrenic, schizophrenics |
| 7 | Neurochem. Int. 2016 Apr -1: -1 |
| PMID | 27129805 |
| 标题 | GLT-1: The elusive presynaptic glutamate transporter. |
| 抽象的 | Historically, glutamate uptake in the CNS was mainly attributed to glial cells for three reasons: 1) none of the glutamate transporters were found to be located in presynaptic terminals of excitatory synapses; 2) the putative glial transporters, GLT-1 and GLAST are expressed at high levels in astrocytes; 3) studies of the constitutive GLT-1 knockout as well as pharmacological studies demonstrated that >90% of glutamate uptake into forebrain synaptosomes is mediated by the operation of GLT-1. Here we summarize the history leading up to the recognition of GLT-1a as a presynaptic glutamate transporter. A major issue now is understanding the physiological and pathophysiological significance of the expression of GLT-1 in presynaptic terminals. To elucidate the cell-type specific functions of GLT-1, a conditional knockout was generated with which to inactivate the GLT-1 gene in different cell types using Cre/LOX技术。星形细胞敲除导致GLT-1表达的80％降低，导致顽固性癫痫发作和早期死亡率，如本构敲除中所示。神经元敲除与没有明显的表型有关。令人惊讶的是，在神经元基因敲除中发现突触体摄取能力（VMAX）显着降低了40％，这表明神经元GLT-1对突触体摄取的贡献与其蛋白质表达（5-10％）不成比例。相反，星形胶质细胞GLT-1对突触体摄取的贡献远低于预期。相比之下，从星形胶质细胞和神经元敲除从脑蛋白制备的脂质体丧失与GLT-1蛋白的丧失相称，这表明突触体制剂中星形胶质细胞中有很大一部分GLT-1的GLT-1不起作用无法重新密封。这些结果表明，需要重新解释许多先前使用突触体摄取来研究谷氨酸运输本身的研究，以及与正常功能，神经变性和对药物反应相关的谷氨酸稳态的变化。 |
| SCZ Keywords | 精神分裂症, schizophrenic, schizophrenics |