| 1 | Harefuah 2004年6月143日：414-6，462 |
|---|---|
| PMID | 15524097 |
| Title | [关于蛋白激酶C与双相情感障碍锂治疗的相关性]。 |
| Abstract | The discovery of lithium's efficacy as a mood-stabilizing agent revolutionized the treatment of patients with bipolar disorder and after 5 decades this drug continues to be the mainstay of treatment of this disorder. Valproate, which is dissimilar structurally to lithium, shares most of the effects of lithium at the level of protein kinase C (PKC). Both drugs reduce the activity of PKC, though via different mechanisms. In comparison to patients with major depressive disorder,精神分裂症，或健康的对照，躁狂患者的PKC活性显着升高，这表明PKC活性的变化可能是疾病的中心病理特征。PKC活性在情绪调节中的精确生理作用尚不清楚。酶通过许多底物蛋白的磷酸化调节细胞反应。PKC的这种底物包括细胞骨架蛋白，神经递质和激素受体，G蛋白，GAP-43，MARCKS等等。需要进一步的研究来阐明CPK变化在双极性疾病中的任何因果作用。 |
| SCZ Keywords | 精神分裂症 |
| 2 | 神经生物醇。dis。2010年12月40日：608-21 |
| PMID | 20699120 |
| Title | Does gene deletion of AMPA GluA1 phenocopy features of schizoaffective disorder? |
| Abstract | Glutamatergic障碍我强烈mplicated in精神分裂症和情绪障碍。GLUA1淘汰（KO）小鼠展示精神分裂症- 与抑郁有关的异常。在这里，我们询问GLUA1 KO是否表现出与躁狂有关的异常。对KO进行了进近/避免冲突测试，对反复游泳暴露的反应以及在压力下和精神刺激治疗后的运动反应测试。锂或GSK-3的快速多巴胺消耗和治疗的影响？测试了抑制剂（SB216763）在KO运动多动症中。结果表明，KO表现出新颖的和压力诱导的运动多动症，降低了强迫游泳的动作以及进近/避免冲突测试的改变。精神刺激治疗和多巴胺耗竭加剧了KO运动多动症。锂，但不能SB216763，治疗将KO焦虑相关的行为标准化，并部分逆转了超子运动的行为，并且磷酸的前额叶皮层水平升高MARCKSand phospho-neuromodulin. Collectively, these findings demonstrate mania-related abnormalities in GluA1 KO and, combined with previous findings, suggest this mutant may provide a novel model of features of schizoaffective disorder. |
| SCZ Keywords | 精神分裂症 |
| 3 | PLoS ONE 2010 -1 5: e8773 |
| PMID | 20098743 |
| Title | 诱发症调节肉豆蔻酰化富含丙氨酸的蛋白激酶C底物的转录水平通过小鼠脑中的NF-YB相互作用。 |
| Abstract | An accumulating body of evidence suggests that Dtnbp1 (Dysbindin) is a key susceptibility gene for精神分裂症。使用酵母 - 两杂交筛查系统，我们检查了与dysbindin相互作用的候选蛋白，并揭示了这些候选者之一是转录因子NF-YB。 我们采用免疫沉淀（IP）测定法来证明异常蛋白-NF-YB相互作用。DNA芯片用于筛选改变基因在dysbindin或nf-YB的细胞中的表达，同时使用染色质IP和报告基因分析来确认这些基因在转录中涉及肉豆蔻酰氨基酰胺富含丙氨酸的富含丙氨酸的蛋白质Cinase C底物（（MARCKS). The sdy mutant mice with a deletion in Dysbindin, which exhibit behavioral abnormalities, and wild-type DBA2J mice were used to investigateMARCKS表达。 We revealed an interaction between Dysbindin and NF-YB. DNA chips showed thatMARCKSexpression was increased in both Dysbindin knockdown cells and NF-YB knockdown cells, and Chromatin IP revealed interaction of these proteins at theMARCKSpromoter region. Reporter assay results suggested functional involvement of the interaction between Dysbindin and NF-YB inMARCKStranscription levels, via the CCAAT motif which is a NF-YB binding sequence.MARCKS与野生型小鼠相比，SDY突变小鼠的表达增加。 These findings suggest that abnormal expression ofMARCKSvia dysfunction of Dysbindin might cause impairment of neural transmission and abnormal synaptogenesis. Our results should provide new insights into the mechanisms of neuronal development and the pathogenesis of精神分裂症。 |
| SCZ Keywords | 精神分裂症 |
| 4 | 摩尔。精神病学2013年12月18日：1249-64 |
| PMID | 23958961 |
| Title | 发现和验证血液生物标志物的自杀性。 |
| Abstract | 自杀事件是psychiatr死亡的主要原因ic patients, and in society at large. Developing more quantitative and objective ways (biomarkers) for predicting and tracking suicidal states would have immediate practical applications and positive societal implications. We undertook such an endeavor. First, building on our previous blood biomarker work in mood disorders and psychosis, we decided to identify blood gene expression biomarkers for suicidality, looking at differential expression of genes in the blood of subjects with a major mood disorder (bipolar disorder), a high-risk population prone to suicidality. We compared no suicidal ideation (SI) states and high SI states using a powerful intrasubject design, as well as an intersubject case-case design, to generate a list of differentially expressed genes. Second, we used a comprehensive Convergent Functional Genomics (CFG) approach to identify and prioritize from the list of differentially expressed gene biomarkers of relevance to suicidality. CFG integrates multiple independent lines of evidence-genetic and functional genomic data-as a Bayesian strategy for identifying and prioritizing findings, reducing the false-positives and false-negatives inherent in each individual approach. Third, we examined whether expression levels of the blood biomarkers identified by us in the live bipolar subject cohort are actually altered in the blood in an age-matched cohort of suicide completers collected from the coroner's office, and report that 13 out of the 41 top CFG scoring biomarkers (32%) show step-wise significant change from no SI to high SI states, and then to the suicide completers group. Six out of them (15%) remained significant after strict Bonferroni correction for multiple comparisons. Fourth, we show that the blood levels of SAT1 (spermidine/spermine N1-acetyltransferase 1), the top biomarker identified by us, at the time of testing for this study, differentiated future as well as past hospitalizations with suicidality, in a live cohort of bipolar disorder subjects, and exhibited a similar but weaker pattern in a live cohort of psychosis (精神分裂症/schizoaffective disorder) subjects. Three other (phosphatase and tensin homolog (PTEN), myristoylated alanine-rich protein kinase C substrate (MARCKS在Bonferroni校正中幸存的六种生物标志物的促丝因激活蛋白激酶激酶激酶3（MAP3K3））表现出相似但较弱的作用。综上所述，前瞻性和回顾性住院数据表明SAT1，PTEN，MARCKSand MAP3K3 might be not only state biomarkers but trait biomarkers as well. Fifth, we show how a multi-dimensional approach using SAT1 blood expression levels and two simple visual-analog scales for anxiety and mood enhances predictions of future hospitalizations for suicidality in the bipolar cohort (receiver-operating characteristic curve with area under the curve of 0.813). Of note, this simple approach does not directly ask about SI, which some individuals may deny or choose not to share with clinicians. Lastly, we conducted bioinformatic analyses to identify biological pathways, mechanisms and medication targets. Overall, suicidality may be underlined, at least in part, by biological mechanisms related to stress, inflammation and apoptosis. |
| SCZ Keywords | 精神分裂症 |
| 5 | 精神分裂。res。2014年4月154日：36-41 |
| PMID | 24568864 |
| Title | 精神分裂症前额叶皮层中肉豆蔻酰氨基酰胺，富含丙氨酸的C激酶底物（MARCKS）的改变。 |
| Abstract | Abnormal synaptic plasticity has been implicated in the cognitive deficits seen in精神分裂症, where alterations have been found in neurotransmission, signaling and dendritic dynamics. Rapid rearrangement of the actin cytoskeleton is critical for plasticity and abnormalities of molecular regulators of this process are candidates for understanding mechanisms underlying these changes in精神分裂症。The myristoylated, alanine-rich C-kinase substrate (MARCKS) is crucial for many roles associated with synaptic plasticity, including facilitation of neurotransmission, dendritic branching and in turn cognitive function. Accordingly, we hypothesized that this protein is abnormally expressed or regulated in精神分裂症。We measured protein expression ofMARCKS通过蛋白质印迹分析，来自老年人的背外侧前额叶皮层（DLPFC）的死后样品精神分裂症患者（n = 16）和比较组（n = 20）。我们还测定了磷酸化 -MARCKS（（pMARCKS), given the role of phosphorylation in reversing membrane association byMARCKS。We found decreased expression of bothMARCKSand pMARCKSin精神分裂症。肉豆蔻酰化的改变可能是一种解释这种下调的机制MARCKS, so we also assayed expression of the two isoforms of the key myristoylation enzyme, NMT, and an enzymatic inhibitor of this enzyme, NMT-inhibitor protein (NIP71) by Western blotting in these same subjects. Expression did not change between groups for these proteins, suggesting a mechanism other than myristoylation is responsible for decreasedMARCKSexpression in精神分裂症。These data suggest a potential mechanism underlying aspects of altered synaptic plasticity observed in精神分裂症。 |
| SCZ Keywords | 精神分裂症 |
| 6 | 精神分裂。res。2015年5月164日：100-8 |
| PMID | 25757715 |
| Title | Altered prefrontal cortical MARCKS and PPP1R9A mRNA expression in schizophrenia and bipolar disorder. |
| Abstract | We previously observed dendritic spine loss in the dorsolateral prefrontal cortex (DLPFC) from精神分裂症和躁郁症受试者。在当前的研究中，我们试图确定已知的基因的mRNA表达是否调节肌动蛋白细胞骨架和脊柱与脊柱损失相关。 Five candidate genes were identified using previously obtained microarray data from the DLPFC from精神分裂症and control subjects. The relative mRNA expression of the genes linked to dendritic spine growth and function, i.e. IGF1R,MARCKS，PPP1R9A，PTPRF和ARHGEF2使用第二个队列中的DLPFC中的定量实时PCR（QRT-PCR）评估，包括精神分裂症，躁郁症和控制受试者。进行了功能途径分析，以确定感兴趣的基因与哪种肌动蛋白细胞骨架调节途径相互作用。 MARCKSmRNA expression was increased in both精神分裂症和躁郁症受试者。PPP1R9A mRNA expression was increased in bipolar disorder subjects. For IGF1R, mRNA expression did not differ significantly among groups; however, it did show a significant, negative correlation with dendrite length.MARCKSand PPP1R9A mRNA expression did not correlate with spine loss, but they interact with NMDA receptor signaling pathways that regulate the actin cytoskeleton and spines. MARCKSPPP1R9A可能会导致脊柱损失精神分裂症and bipolar disorder through their interactions, possibly indirect ones, with NMDA signaling pathways that regulate spine structure and function. |
| SCZ Keywords | 精神分裂症 |