| 1 | Neurochem. Res. 2013 Jun 38: 1134-43 |
|---|---|
| PMID | 23354723 |
| 标题 | 多氨酸：NCAM，SynCAM 1和Neuropilin-2的多功能修饰。 |
| 抽象的 | 的多糖polysialic酸是众所周知的a unique posttranslational modification of the neural cell adhesion molecule NCAM. Despite remarkable acceptor specificity, however, a few other proteins can be targets of polysialylation. Here, we recapitulate the biosynthesis of polysialic acid by the two polysialyltransferases ST8SIA2 andST8SIA4并强调了越来越多的证据表明，人类ST8SIA2基因的变化与schizophreniaand possibly other neuropsychiatric disorders. Moreover, we summarize the knowledge on the role of NCAM polysialylation in brain development gained by the analysis of NCAM- and polysialyltransferase-deficient mouse models. The last part of this review is focused on recent advances in identifying SynCAM 1 and neuropilin-2 as novel acceptors of polysialic acid in NG2 cells of the perinatal brain and in dendritic cells of the immune system, respectively. |
| SCZ关键字 | schizophrenia |
| 2 | Development 2014 Aug 141: 3022-32 |
| PMID | 24993945 |
| 标题 | A crucial role for polysialic acid in developmental interneuron migration and the establishment of interneuron densities in the mouse prefrontal cortex. |
| 抽象的 | 多氨酸（polysia）是神经细胞粘附分子NCAM的独特聚糖修饰，也是脑发育的主要决定因素。NCAM的多晶酰化由两个多溶解酶（Polysts）ST8SIA2和ST8SIA4。Dysregulation of the polySia-NCAM system and variation in ST8SIA2 has been linked toschizophreniaand other psychiatric disorders. Here, we show reduced interneuron densities in the medial prefrontal cortex (mPFC) of mice with either partial or complete loss of polySia synthesizing capacity by ablation of St8sia2,ST8SIA4, or both. Cells positive for parvalbumin and perineuronal nets as well as somatostatin-positive cells were reduced in the mPFC of all polyST-deficient lines, whereas calretinin-positive cells and the parvalbumin-negative fraction of calbindin-positive cells were unaffected. Reduced interneuron numbers were corroborated by analyzing polyST-deficient GAD67-GFP knock-in mice. The accumulation of precursors in the ganglionic eminences and reduced numbers of tangentially migrating interneurons in the pallium were observed in polyST-deficient embryos. Removal of polySia by endosialidase treatment of organotypic slice cultures led to decreased entry of GAD67-GFP-positive interneurons from the ganglionic eminences into the pallium. Moreover, the acute loss of polySia caused significant reductions in interneuron velocity and leading process length. Thus, attenuation of polySia interferes with the developmental migration of cortical interneurons and causes pathological changes in specific interneuron subtypes. This provides a possible link between genetic variation in polyST genes, neurodevelopmental alterations and interneuron dysfunction in neuropsychiatric disease. |
| SCZ关键字 | schizophrenia |
| 3 | Brain Struct函数2015年1月220日：71-83 |
| PMID | 24057454 |
| 标题 | Schizophrenia-like phenotype of polysialyltransferase ST8SIA2-deficient mice. |
| 抽象的 | Posttranslational modification of the neural cell adhesion molecule (NCAM) by polysialic acid (polySia) is crucial for nervous system development and brain plasticity. PolySia attachment is catalyzed by the polysialyltransferases (polySTs) ST8SIA2 andST8SIA4，在神经发育和成年大脑过程中具有独特但共同功能的两种酶。越来越多的证据将NCAM和Polysia的异常水平以及ST8SIA2基因的变异与神经精神疾病有关，包括schizophrenia。调查polyst缺乏是否可能导致schizophrenia-like phenotype, St8sia2 (-/-) mice,ST8SIA4（ - / - ）小鼠及其野生型同窝仔进行神经解剖学评估，并进行认知和感觉运动功能的测试。ST8SIA2（ - / - ），但没有ST8SIA4（ - / - ）小鼠表现出扩大的侧心室，丘脑的尺寸减小，伴随着较小的内部胶囊和连接丘脑和皮质的纤维的高度混乱的纤维图案。降低的囊泡谷氨酸转运蛋白VGLUT2的水平降低了指向谷氨酸丘脑皮质皮质输入损害到ST8SIA2（ - / - ）小鼠的额叶皮质中。在短期和长期识别记忆中，两种多缺陷线都受损，但是只有ST8SIA2（ - / - ）小鼠在预硫抑制中显示出受损的工作记忆和缺陷。此外，只有ST8SIA2（ - / - ）小鼠表现出对苯丙胺诱导的超倒态剂的敏感性的表现，并提高了敏感性。这些结果表明，在ST8SIA2（ - / - ）小鼠中降低的多磷酸导致病理学脑发育和schizophrenia-like behavior. We therefore propose that genetic variation in ST8SIA2 has the potential to confer a neurodevelopmental predisposition toschizophrenia。 |
| SCZ关键字 | schizophrenia |
| 4 | 精神分裂。res。2016年3月-1：-1 |
| PMID | 26972474 |
| 标题 | 精神分裂症前额叶皮质中类蛋白酶和生长抑素神经元的发育调节剂的表达改变。 |
| 抽象的 | 前额叶皮层（PFC）抑制性神经元的功能障碍，该神经元表达钙结合蛋白白蛋白或神经肽生长抑素在schizophreniamay be related to disturbances in the migration, phenotypic specification, and/or maturation of these neurons. These pre- and postnatal developmental stages are regulated in a cell type-specific manner by various transcription factors and co-activators, fibroblast growth factor receptors (FgfR), and other molecular markers. Consequently, we used quantitative PCR to quantify mRNA levels for these developmental regulators in the PFC of 62schizophreniasubjects in whom parvalbumin and somatostatin neuron disturbances were previously reported, and in antipsychotic-exposed monkeys. Relative to unaffected comparison subjects, subjects withschizophreniaexhibited elevated mRNA levels for 1) the transcription factor MafB, which is expressed by parvalbumin and somatostatin neurons as they migrate from the medial ganglionic eminence to the cortex, 2) the transcriptional coactivator PGC-1?, which is expressed postnatally by parvalbumin neurons to maintain parvalbumin levels and inhibitory function, and 3) FgfR1, which is required for the migration and phenotypic specification of parvalbumin and somatostatin neurons. Elevations in these markers were most prominent in youngerschizophrenia受试者且不存在于抗精神病药暴露的猴子中。最后，其他重要发育调节剂的表达水平（即DLX1，DLX5，DLX6，SATB1，SIP1/ZEB2，ST8SIA4, cMaf, Nkx6.2, and Arx) were not altered inschizophrenia。分子标记子集的过表达在白蛋白和生长抑素神经元的产后和产后发育中具有明显作用，这可能反映出在面对其他侮辱时维持这些神经元发展的补偿机制。 |
| SCZ关键字 | schizophrenia |