| 1 | Neuropsychopharmacology 2008 Nov 33: 2993-3009 |
|---|---|
| PMID | 18322470 |
| 标题 | Abnormal indices of cell cycle activity in schizophrenia and their potential association with oligodendrocytes. |
| 抽象的 | The goal of this study was to determine what signaling pathways may elicit myelin-specific gene expression deficits inschizophrenia(SZ). Microarray analyses indicated that genes associated with canonical cell cycle pathways were significantly affected in the anterior cingulate gyrus (ACG), the region exhibiting the most profound myelin-specific gene expression changes, in persons with SZ (N=16) as compared with controls (N=19). Detected gene expression changes of key regulators of G1/S phase transition and genes central to oligodendrocyte differentiation were validated using qPCR in the ACG in an independent cohort (Ns=45/34). The relative abundance of phosphorylated retinoblastoma protein (pRb) was increased in the white matter underlying the ACG in SZ subjects (Ns=12). The upregulation of cyclin D1 gene expression and the downregulation of p57(Kip2), accompanied by increased cyclin D/CDK4-dependent phosphorylation of pRb, acting as a checkpoint for G1/S phase transition, suggest abnormal cell cycle re-entry in postmitotic oligodendrocytes in SZ. Furthermore, gene expression profiling of brain samples from myelin mutant animal models, quaking and myelin-associated glycoprotein (MAG) null mice, showed that cell cycle gene expression changes were not a necessary consequence of the reduced gene expression of structural myelin proteins, such as MAG. While, quaking, a known modulator of cell cycle activity during oligodendrocyte differentiation impairs the expression of multiple myelin genes, including those that are affected in SZ. These data suggest that the normal patterns of cell cycle gene and protein expression are disrupted in SZ and that this disruption may contribute to the oligodendroglial deficits observed in SZ. |
| SCZ关键字 | schizophrenia |
| 2 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2016 May 70: 85-91 |
| PMID | 27216283 |
| 标题 | 与细胞周期相关的基因作为精神分裂症的生物标志物。 |
| 抽象的 | 最近的研究表明，基因组异常，例如单核苷酸多态性（SNP）和拷贝数变化（CNV）可能会提高患有的风险schizophrenia。这种基因组异常经常在细胞周期的S期染色体DNA复制过程中发生。此外，一些研究表明，几个与细胞周期相关基因的异常表达与schizophrenia。Therefore, here we compared mRNA expression levels of cell cycle-related genes in peripheral blood cells between patients withschizophreniaand healthy controls. 信使rna表达的细胞cycle-relate水平d genes in peripheral blood cells from patients withschizophreniaand healthy controls were measured with quantitative reverse transcription polymerase chain reaction (Q-RT-PCR). The discovery, replication and intervention studies with Q-RT-PCR were performed as follows: discovery (40 cases and 20 controls), replication (82 cases and 74 controls) and intervention (22 cases and 18 controls). 在发现和复制阶段确定了九个基因为schizophrenia-associated genes. Moreover, the combination of mRNA expression levels ofCDK4，MCM7和Pold4被确定为潜在的生物标志物schizophreniawith multivariate logistic regression analysis. The intervention stage revealed that the mRNA expression levels of these three genes were significantly decreased in the acute state ofschizophrenia, andCDK4was significantly recovered in the remission state ofschizophrenia。 The combination of mRNA expression levels of three cell cycle-related genes such asCDK4，MCM7和Pold4有望成为有用的生物标志物的候选者schizophrenia。Especially, the mRNA expression changes ofCDK4may be potential as both trait and state markers forschizophrenia。 |
| SCZ关键字 | schizophrenia |
| 3 | Biochim. Biophys. Acta 2016 Aug 1862: 1383-91 |
| PMID | 27130439 |
| 标题 | Schizophrenia susceptibility gene product dysbindin-1 regulates the homeostasis of cyclin D1. |
| 抽象的 | Dysbindin-1 (dystrobrevin binding protein-1, DTNBP1) is now widely accepted as a potentialschizophreniasusceptibility gene and accumulating evidence indicates its functions in the neural development. In this study, we tried to identify new binding partners for dysbindin-1 to clarify the novel function of this molecule. When consulted with BioGRID protein interaction database, cyclin D3 was found to be a possible binding partner for dysbindin-1. We then examined the interaction between various dysbindin-1 isoforms (dysbindin-1A, -1B and -1C) and all three D-type cyclins (cyclin D1, D2, and D3) by immunoprecipitation with the COS7 cell expression system, and found that dysbindin-1A preferentially interacts with cyclin D1. The mode of interaction between these molecules was considered as direct binding since recombinant dysbindin-1A and cyclin D1 formed a complex in vitro. Mapping analyses revealed that the C-terminal region of dysbindin-1A binds to the C-terminal of cyclin D1. Consistent with the results of the biochemical analyses, endogenous dysbindin-1was partially colocalized with cyclin D1 in NIH3T3 fibroblast cells and in neuronal stem and/or progenitor cells in embryonic mouse brain. While co-expression of dysbindin-1A with cyclin D1 changed the localization of the latter from the nucleus to cytosol, cyclin D1-binding partnerCDK4抑制了诱发蛋白 - 环蛋白D1相互作用。同时，内源性症障碍蛋白1a的耗竭增加了细胞周期蛋白D1的表达。这些结果表明，dysbindin-1a可能会控制细胞周期蛋白D1函数时空，并可能有助于更好地理解异育素1相关疾病的病理生理学。 |
| SCZ关键字 | schizophrenia |