| 1 | BMC Res Notes 2012 -1 5：146 |
|---|---|
| PMID | 22420779 |
| Title | 选择性反应监测的应用证实了精神分裂症临床前模型中糖酵解的失调。 |
| Abstract | 建立临床前模型对于新颖的药物发现至关重要精神分裂症。大多数现有模型的特征是行为读数异常，这些读数内容丰富，但不一定转化为人类疾病的症状。因此，有必要从分子的角度表征临床前模型。选择性反应监测（SRM）已经在临床前和临床研究中显示出对诊断，预后和治疗相关生物标志物的多重测量的希望。 We have established an SRM assay for multiplex analysis of 7 enzymes of the glycolysis pathway which is already known to be affected in human精神分裂症并在广泛使用的急性PCP大鼠模型中精神分裂症。The selected enzymes were hexokinase 1 (HK1), aldolase C (Aldoc), triosephosphate isomerase (Tpi1), glyceraldehyde-3-phosphate dehydrogenase (Gapdh), phosphoglycerate mutase 1 (Pgam1), phosphoglycerate kinase 1 (Pgk1) and enolase 2 (Eno2). The levels of these enzymes were analyzed using SRM in frontal cortex from brain tissue of PCP treated rats. 单变量分析显示TPI1水平的统计学显着变化和变化HK1，与对照组相比，PCP大鼠的ALDOC，PGAM1和GAPDH在PCP大鼠中具有边缘意义。最有趣的是，同时考虑所有7种酶的水平的多元分析导致生成双维图，该图表可以将PCP大鼠与对照组区分开。 这项研究不仅支持PCP处理的大鼠作为有用的临床前模型精神分裂症，但它还确定了SRM质谱法可以用于开发用于复杂精神疾病的多重分类工具，例如精神分裂症。 |
| SCZ Keywords | 精神分裂症 |
| 2 | J Psychiatr Res 2012 Jan 46: 95-104 |
| PMID | 22018957 |
| Title | Mitochondrial detachment of hexokinase 1 in mood and psychotic disorders: implications for brain energy metabolism and neurotrophic signaling. |
| Abstract | 情绪和精神病的病理生理学，包括单极抑郁症（UPD），躁郁症（BPD）和精神分裂症(SCHZ), is largely unknown. Numerous studies, from molecular to neuroimaging, indicate that some individuals with these disorders have impaired brain energy metabolism evidenced by abnormal glucose metabolism and mitochondrial dysfunction. However, underlying mechanisms are unclear. A critical feature of brain energy metabolism is attachment to the outer mitochondrial membrane (OMM) of hexokinase 1 (HK1），糖酵解的初始和限速酶。HK1对OMM的依恋极大地增强HK1酶活性和伴侣的胞质糖酵解与线粒体氧化磷酸化，细胞通过其大部分三磷酸腺苷（ATP）。HK1线粒体附着通过预防凋亡和氧化损伤，对神经元和其他细胞的存活也很重要。在这里我们首次显示HK1与没有精神病的对照组相比，与upd，bpd和schz的个体的尸体皮层脑组织的附着相比此外，我们表明HK1线粒体脱离与葡萄糖代谢的替代性的厌氧途径的活性增加有关。这些发现是在无药和无药个体的样本中观察到的。我们提出了这一点HK1线粒体脱离可以通过能量代谢受损，增加对氧化应激的脆弱性以及脑生长和发育受损而与这些疾病有关。 |
| SCZ Keywords | 精神分裂症 |
| 3 | Schizophr. Res. 2014 Apr 154: 1-13 |
| PMID | 24560881 |
| Title | 己糖激酶1的异常分配表明精神分裂症中谷氨酸转运蛋白复合物的破坏。 |
| Abstract | 兴奋性氨基酸转运蛋白2（EAAT2）属于Na（+）依赖性谷氨酸转运蛋白的家族，该家族通过将突触lutamamate从突触left裂中移除到星形胶质细胞和神经元中，从而保持谷氨酸的突触浓度较低。EAAT2活性取决于Na（+）/K（+）ATPase和ATP产生的Na（+）和K（+）梯度。己糖酶1（HK1), an initial enzyme of glycolysis, binds to mitochondrial outer membrane where it couples cytosolic glycolysis to mitochondrial oxidative phosphorylation, producing ATP utilized by the EAAT2/Na(+)/K(+) ATPase protein complex to facilitate glutamate reuptake. In this study, we hypothesized that the protein complex formed by EAAT2, Na(+)/K(+) ATPase and mitochondrial proteins in human postmortem prefrontal cortex may be disrupted, leading to abnormal glutamate transmission in精神分裂症。We first determined that EAAT2, Na(+)/K(+) ATPase,HK1and aconitase were found in both EAAT2 and Na(+)/K(+) ATPase interactomes by immunoisolation and mass spectrometry in human postmortem prefrontal cortex. Next, we measured levels of glutamate transport complex proteins in subcellular fractions in the dorsolateral prefrontal cortex and found increases in the EAAT2B isoform of EAAT2 in a fraction containing extrasynaptic membranes and increased aconitase 1 in a mitochondrial fraction. Finally, an increased ratio ofHK1在患有受试者的受试者中发现了突触外膜/线粒体级分中的蛋白质精神分裂症, suggesting thatHK1蛋白质在这种疾病中受到异常分区。我们的发现表明，谷氨酸转运蛋白复合物的完整性可能会破坏，从而导致谷氨酸的环节缓冲和再摄取减少，以及在能量代谢中受损精神分裂症。 |
| SCZ Keywords | 精神分裂症 |
| 4 | 前细胞Neurosci 2015 -1 9：180 |
| PMID | 26029051 |
| Title | MK-801 treatment affects glycolysis in oligodendrocytes more than in astrocytes and neuronal cells: insights for schizophrenia. |
| Abstract | 精神分裂症是一种使人衰弱的精神障碍，影响了全球超过3000万人。作为多因素疾病，是精神分裂症require analysis by multiplex methods such as proteomics to allow identification of whole protein networks. Previous post-mortem proteomic studies on brain tissues from精神分裂症病人已经证明了激活o的变化f glycolytic and energy metabolism pathways. However, it is not known whether these changes occur in neurons or in glial cells. To address this question, we treated neuronal, astrocyte, and oligodendrocyte cell lines with the NMDA receptor antagonist MK-801 and measured the levels of six glycolytic enzymes by Western blot analysis. MK-801 acts on the glutamatergic system and has been proposed as a pharmacological means of modeling精神分裂症。用MK-801处理导致所有细胞类型中的糖酵解酶水平发生显着变化。大多数差异都是在少突胶质细胞中发现的，这改变了己糖苷酶1的水平（HK1），烯醇酶2（ENO2），磷酸甘油酸激酶（PGK）和急性MK-801治疗后（8 h）和HK1长期治疗后（72 h）后，，ENO2，PGK和三氧磷酸异构酶（TPI）。在培养物中添加抗精神病药氯氮平在MK-801治疗中通过使ENO2和PGK的水平在急性和长期培养物中标准化，从而对MK-801的治疗产生了反调节作用。在星形胶质细胞中，MK-801在急性条件和HK1and ALDOC following long term treatment, and TPI was the only enzyme affected under long term conditions in the neuronal cells. In conclusion, MK-801 affects glycolysis in oligodendrocytes to a larger extent than neuronal cells and this may be modulated by antipsychotic treatment. Although cell culture studies do not necessarily reflect the in vivo pathophysiology and drug effects within the brain, these results suggest that neurons, astrocytes, and oligodendrocytes are affected differently in精神分裂症。使用神经递质激动剂和拮抗剂采用体外模型可能会提供有关病理生理学的新见解精神分裂症这可能导致一种新型的药物发现系统。 |
| SCZ Keywords | 精神分裂症 |