| 1 | PLoS ONE 2007 -1 2: e817 |
|---|---|
| PMID | 17786189 |
| Title | Sp1 expression is disrupted in schizophrenia; a possible mechanism for the abnormal expression of mitochondrial complex I genes, NDUFV1 and NDUFV2. |
| Abstract | The prevailing hypothesis regardsschizophreniaas a polygenic disease, in which multiple genes combine with each other and with environmental stimuli to produce the variance of its clinical symptoms. We investigated whether the ubiquitous transcription factor Sp1 is abnormally expressed inschizophrenia, and consequently can affect the expression of genes implicated in this disorder. mRNA of Sp1 and of mitochondrial complex I subunits (NDUFV1, NDUFV2) was analyzed in three postmortem brain regions obtained from the Stanley Foundation Brain Collection, and in lymphocytes ofschizophrenicpatients and controls. Sp1 role in the transcription of these genes was studied as well. Sp1 was abnormally expressed inschizophrenia在大脑和周围。它的mRNA改变模式与NDUFV1and NDUFV2, decreasing in the prefrontal cortex and the striatum, while increasing in the parieto-occipital cortex and in lymphocytes ofschizophrenicpatients as compared with controls. Moreover, a high and significant correlation between these genes existed in normal subjects, but was distorted in patients. Sp1 role in the regulation of complex I subunits, was demonstrated by the ability of the Sp1/DNA binding inhibitor, mithramycin, to inhibit the transcription ofNDUFV1and NDUFV2, in neuroblastoma cells. In addition, Sp1 activated NDUFV2 promoter by binding to its three GC-boxes. Both activation and binding were inhibited by mithramycin. 这些发现表明，SP1中的异常可以是主要的激活因子/阻遏物或与其他转录因子结合起作用并受到环境刺激的作用，可能有助于多基因和临床上异质性的性质schizophrenia. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 2 | PLoS ONE 2007 -1 2: e817 |
| PMID | 17786189 |
| Title | Sp1 expression is disrupted in schizophrenia; a possible mechanism for the abnormal expression of mitochondrial complex I genes, NDUFV1 and NDUFV2. |
| Abstract | The prevailing hypothesis regardsschizophreniaas a polygenic disease, in which multiple genes combine with each other and with environmental stimuli to produce the variance of its clinical symptoms. We investigated whether the ubiquitous transcription factor Sp1 is abnormally expressed inschizophrenia, and consequently can affect the expression of genes implicated in this disorder. mRNA of Sp1 and of mitochondrial complex I subunits (NDUFV1, NDUFV2) was analyzed in three postmortem brain regions obtained from the Stanley Foundation Brain Collection, and in lymphocytes ofschizophrenicpatients and controls. Sp1 role in the transcription of these genes was studied as well. Sp1 was abnormally expressed inschizophrenia在大脑和周围。它的mRNA改变模式与NDUFV1and NDUFV2, decreasing in the prefrontal cortex and the striatum, while increasing in the parieto-occipital cortex and in lymphocytes ofschizophrenicpatients as compared with controls. Moreover, a high and significant correlation between these genes existed in normal subjects, but was distorted in patients. Sp1 role in the regulation of complex I subunits, was demonstrated by the ability of the Sp1/DNA binding inhibitor, mithramycin, to inhibit the transcription ofNDUFV1and NDUFV2, in neuroblastoma cells. In addition, Sp1 activated NDUFV2 promoter by binding to its three GC-boxes. Both activation and binding were inhibited by mithramycin. 这些发现表明，SP1中的异常可以是主要的激活因子/阻遏物或与其他转录因子结合起作用并受到环境刺激的作用，可能有助于多基因和临床上异质性的性质schizophrenia. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 3 | PLoS ONE 2008 -1 3: e3676 |
| PMID | 18989376 |
| Title | Neuroanatomical pattern of mitochondrial complex I pathology varies between schizophrenia, bipolar disorder and major depression. |
| Abstract | Mitochondrial dysfunction was reported inschizophrenia, bipolar disorderand major depression. The present study investigated whether mitochondrial complex I abnormalities show disease-specific characteristics. mRNA and protein levels of complex I subunitsNDUFV1, NDUFV2 and NADUFS1, were assessed in striatal and lateral cerebellar hemisphere postmortem specimens and analyzed together with our previous data from prefrontal and parieto-occipital cortices specimens of patients withschizophrenia, bipolar disorder, major depression and healthy subjects. A disease-specific anatomical pattern in complex I subunits alterations was found.schizophrenia-specific reductions were observed in the prefrontal cortex and in the striatum. The depressed group showed consistent reductions in all three subunits in the cerebellum. The bipolar group, however, showed increased expression in the parieto-occipital cortex, similar to those observed inschizophrenia, and reductions in the cerebellum, yet less consistent than the depressed group. These results suggest that the neuroanatomical pattern of complex I pathology parallels the diversity and similarities in clinical symptoms of these mental disorders. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 4 | J Mol Psychiatry 2014 -1 2: 6 |
| PMID | 25713723 |
| Title | 精神分裂症中的线粒体复合物I和III基因mRNA水平及其与临床特征的关系。 |
| Abstract | The etiology ofschizophreniais not precisely known; however, mitochondrial function and cerebral energy metabolism abnormalities were determined to be possible factors associated with the etiology ofschizophrenia. Impaired mitochondrial function negatively affects neuronal plasticity, and can cause cognitive deficits and behavioral abnormalities observed during the clinical course ofschizophrenia. The present study aimed to investigate the relationship between the clinical features ofschizophrenia, and mitochondrial complex activation, based on measurement of mRNA levels in theNDUFV1、NDUFV2 NDUFS1, UQCR10基因in the peripheral mitochondrial complex. The study included 138schizophreniapatients and 42 healthy controls. Theschizophreniagroup was divided into a chronicschizophreniasubgroup (n?=?84) and a first-episodeschizophreniasubgroup (n?=?54). The symptoms profile and severity of disorder were evaluated using the Scale for the Assessment of Negative Symptoms (SANS), Scale for the Assessment of Positive Symptoms (SAPS), and Brief Psychiatric Rating Scale (BPRS). The level of mRNA expression ofNDUFV1, NDUFV2, and NDUFS1 was significantly higher in theschizophreniagroup than in the control group. The mRNA level of NDUFV2 was positively correlated with BPRS and SAPS scores in the first-episodeschizophreniasubgroup. The findings showed that there was a positive correlation between gene mRNA levels and psychotic symptomatology, especially positive symptoms. Our results suggest that mRNA levels of theNDUFV1, NUDFV2, and NDUFS1 genes of complex I of the mitochondrial electron transport chain might become a possible peripheral marker for the diagnosis ofschizophrenia. |
| SCZ关键字 | 精神分裂症，精神分裂症 |