| 1 | Int. J. Neuropsychopharmacol. 2005 Dec 8: 515-22 |
|---|---|
| PMID | 16202181 |
| Title | Quantitative analysis of mitochondrial DNA deletions in the brains of patients with bipolar disorder and schizophrenia. |
| Abstract | Several clinical, genetic and neuroimaging studies implicate mitochondrial dysfunction in the pathophysiology of bipolar disorder andschizophrenia. It has been reported that a mitochondrial DNA (mtDNA) deletion of 4,977 bp, known as the 'common deletion', is associated with both mental illnesses. A lack of normal age-related accumulation of this deletion inschizophreniaand increased occurrence of the common deletion in bipolar disorder have been reported. However, even in the affected bipolar samples, the levels of common deletion were relatively small, indicating that the common deletion did not play a pathophysiological role in respiratory function. We hypothesized that accumulation of multiple mtDNA deletions, rather than the common deletion alone, is involved in the pathophysiology of these two major mental disorders. To test this hypothesis, we assessed mtDNA deletion(s) by comparing the copy number of two regions in mtDNA --ND1and ND4 -- using real-time quantitative PCR in the frontal cortex of 84 subjects (30 control, 27 with bipolar disorder, and 27 withschizophrenia). We also assessed the relative amount of mtDNA vs. nuclear DNA and the expression level of DNA polymerase gamma (POLG), which is involved in replicating mtDNA. We observed no association between mtDNA deletions and the two major mental disorders in the frontal cortex, which did not support our hypothesis. We did, however, make the following observations, although they were not significant after Bonferroni correction: (1) the ratio of mtDNA to nuclear DNA was significantly higher in female patients withschizophreniathan in control females ( p =0.040) and (2) in bipolar disorder, the relative amount of mtDNA decreased with age ( p =0.016). furthermore, POLG expression was significantly up-regulated in bipolar disorder ( p =0.036). Our results suggest that abnormalities in the system maintaining replication of mtdna may underlie bipolar disorder andschizophrenia. |
| SCZ Keywords | schizophrenia |
| 2 | Int. J. Neuropsychopharmacol. 2005 Dec 8: 515-22 |
| PMID | 16202181 |
| Title | Quantitative analysis of mitochondrial DNA deletions in the brains of patients with bipolar disorder and schizophrenia. |
| Abstract | Several clinical, genetic and neuroimaging studies implicate mitochondrial dysfunction in the pathophysiology of bipolar disorder andschizophrenia. It has been reported that a mitochondrial DNA (mtDNA) deletion of 4,977 bp, known as the 'common deletion', is associated with both mental illnesses. A lack of normal age-related accumulation of this deletion inschizophreniaand increased occurrence of the common deletion in bipolar disorder have been reported. However, even in the affected bipolar samples, the levels of common deletion were relatively small, indicating that the common deletion did not play a pathophysiological role in respiratory function. We hypothesized that accumulation of multiple mtDNA deletions, rather than the common deletion alone, is involved in the pathophysiology of these two major mental disorders. To test this hypothesis, we assessed mtDNA deletion(s) by comparing the copy number of two regions in mtDNA --ND1and ND4 -- using real-time quantitative PCR in the frontal cortex of 84 subjects (30 control, 27 with bipolar disorder, and 27 withschizophrenia). We also assessed the relative amount of mtDNA vs. nuclear DNA and the expression level of DNA polymerase gamma (POLG), which is involved in replicating mtDNA. We observed no association between mtDNA deletions and the two major mental disorders in the frontal cortex, which did not support our hypothesis. We did, however, make the following observations, although they were not significant after Bonferroni correction: (1) the ratio of mtDNA to nuclear DNA was significantly higher in female patients withschizophreniathan in control females ( p =0.040) and (2) in bipolar disorder, the relative amount of mtDNA decreased with age ( p =0.016). furthermore, POLG expression was significantly up-regulated in bipolar disorder ( p =0.036). Our results suggest that abnormalities in the system maintaining replication of mtdna may underlie bipolar disorder andschizophrenia. |
| SCZ Keywords | schizophrenia |
| 3 | Int. J. Neuropsychopharmacol. 2005 Dec 8: 515-22 |
| PMID | 16202181 |
| Title | Quantitative analysis of mitochondrial DNA deletions in the brains of patients with bipolar disorder and schizophrenia. |
| Abstract | Several clinical, genetic and neuroimaging studies implicate mitochondrial dysfunction in the pathophysiology of bipolar disorder andschizophrenia. It has been reported that a mitochondrial DNA (mtDNA) deletion of 4,977 bp, known as the 'common deletion', is associated with both mental illnesses. A lack of normal age-related accumulation of this deletion inschizophreniaand increased occurrence of the common deletion in bipolar disorder have been reported. However, even in the affected bipolar samples, the levels of common deletion were relatively small, indicating that the common deletion did not play a pathophysiological role in respiratory function. We hypothesized that accumulation of multiple mtDNA deletions, rather than the common deletion alone, is involved in the pathophysiology of these two major mental disorders. To test this hypothesis, we assessed mtDNA deletion(s) by comparing the copy number of two regions in mtDNA --ND1and ND4 -- using real-time quantitative PCR in the frontal cortex of 84 subjects (30 control, 27 with bipolar disorder, and 27 withschizophrenia). We also assessed the relative amount of mtDNA vs. nuclear DNA and the expression level of DNA polymerase gamma (POLG), which is involved in replicating mtDNA. We observed no association between mtDNA deletions and the two major mental disorders in the frontal cortex, which did not support our hypothesis. We did, however, make the following observations, although they were not significant after Bonferroni correction: (1) the ratio of mtDNA to nuclear DNA was significantly higher in female patients withschizophreniathan in control females ( p =0.040) and (2) in bipolar disorder, the relative amount of mtDNA decreased with age ( p =0.016). furthermore, POLG expression was significantly up-regulated in bipolar disorder ( p =0.036). Our results suggest that abnormalities in the system maintaining replication of mtdna may underlie bipolar disorder andschizophrenia. |
| SCZ Keywords | schizophrenia |
| 4 | Nihon Shinkei Seishin Yakurigaku Zasshi 2007 Jun 27: 103-7 |
| PMID | 17633521 |
| Title | [Spine biology in psychiatric diseases]. |
| Abstract | Local translation near or in spines is thought to be a molecular basis of synaptic plasticity and its abnormalities may cause psychiatric diseases. The RNA binding protein, TLS, which is identified from a screening by using a pharmacological model forschizophrenia, is translocated to dendritic spines by mGluR5 activation and regulates spine morphology. TLS facilitates transport of mRNA encoding an actin-stabilizing protein,ND1-L, to dendritic spines. Moreover, myosin-Va is essential for the accumulation of TLS and its target RNA,ND1-L, in dendritic spines. |
| SCZ Keywords | schizophrenia |
| 5 | Nihon Shinkei Seishin Yakurigaku Zasshi 2007 Jun 27: 103-7 |
| PMID | 17633521 |
| Title | [Spine biology in psychiatric diseases]. |
| Abstract | Local translation near or in spines is thought to be a molecular basis of synaptic plasticity and its abnormalities may cause psychiatric diseases. The RNA binding protein, TLS, which is identified from a screening by using a pharmacological model forschizophrenia, is translocated to dendritic spines by mGluR5 activation and regulates spine morphology. TLS facilitates transport of mRNA encoding an actin-stabilizing protein,ND1-L, to dendritic spines. Moreover, myosin-Va is essential for the accumulation of TLS and its target RNA,ND1-L, in dendritic spines. |
| SCZ Keywords | schizophrenia |
| 6 | Nihon Shinkei Seishin Yakurigaku Zasshi 2007 Jun 27: 103-7 |
| PMID | 17633521 |
| Title | [Spine biology in psychiatric diseases]. |
| Abstract | Local translation near or in spines is thought to be a molecular basis of synaptic plasticity and its abnormalities may cause psychiatric diseases. The RNA binding protein, TLS, which is identified from a screening by using a pharmacological model forschizophrenia, is translocated to dendritic spines by mGluR5 activation and regulates spine morphology. TLS facilitates transport of mRNA encoding an actin-stabilizing protein,ND1-L, to dendritic spines. Moreover, myosin-Va is essential for the accumulation of TLS and its target RNA,ND1-L, in dendritic spines. |
| SCZ Keywords | schizophrenia |
| 7 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2013 Mar 162B: 213-23 |
| PMID | 23355257 |
| Title | 线粒体DNA (mtDNA) in brain samples from patients with major psychiatric disorders: gene expression profiles, mtDNA content and presence of the mtDNA common deletion. |
| Abstract | Several lines of evidence support a mitochondrial dysfunction in major psychiatric disorders. The objective of this study was to determine whether mitochondrial DNA (mtDNA) expression or content are implicated in the mitochondrial dysfunction observed inschizophrenia(SCH), bipolar disorder (BD), and major depressive disorder (MDD). MtDNA gene expression and mtDNA content (including the MT-ND4 deletion) were measured by RT-qPCR and qPCR, respectively. Post-mortem brain tissue from 60 subjects, divided evenly into four diagnostic groups (SCH, BD, MDD, and control (C)), was analyzed. MT-ND1gene expression was significantly increased in the BD group compared with the C group. MDD and SCH patients showed a similar pattern of mtDNA expression, which was different from that in BD patients. Similarly, a larger number of MDD and SCH patients tended to have the MT-ND4 gene deleted compared with BD and C subjects. However, no other significant differences were observed in mtDNA gene expression and mtDNA content. Notably, high variability was observed in the mtDNA gene expression and content in each diagnostic group. Previous studies and the present work provide evidence for a role of mtDNA in SCH, BD and MDD. However, further studies with larger patient and control groups as well as by analyzing distinct brain regions are needed to elucidate the role of mtDNA in major psychiatric disorders. |
| SCZ Keywords | schizophrenia |
| 8 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2013 Mar 162B: 213-23 |
| PMID | 23355257 |
| Title | 线粒体DNA (mtDNA) in brain samples from patients with major psychiatric disorders: gene expression profiles, mtDNA content and presence of the mtDNA common deletion. |
| Abstract | Several lines of evidence support a mitochondrial dysfunction in major psychiatric disorders. The objective of this study was to determine whether mitochondrial DNA (mtDNA) expression or content are implicated in the mitochondrial dysfunction observed inschizophrenia(SCH), bipolar disorder (BD), and major depressive disorder (MDD). MtDNA gene expression and mtDNA content (including the MT-ND4 deletion) were measured by RT-qPCR and qPCR, respectively. Post-mortem brain tissue from 60 subjects, divided evenly into four diagnostic groups (SCH, BD, MDD, and control (C)), was analyzed. MT-ND1gene expression was significantly increased in the BD group compared with the C group. MDD and SCH patients showed a similar pattern of mtDNA expression, which was different from that in BD patients. Similarly, a larger number of MDD and SCH patients tended to have the MT-ND4 gene deleted compared with BD and C subjects. However, no other significant differences were observed in mtDNA gene expression and mtDNA content. Notably, high variability was observed in the mtDNA gene expression and content in each diagnostic group. Previous studies and the present work provide evidence for a role of mtDNA in SCH, BD and MDD. However, further studies with larger patient and control groups as well as by analyzing distinct brain regions are needed to elucidate the role of mtDNA in major psychiatric disorders. |
| SCZ Keywords | schizophrenia |
| 9 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2013 Mar 162B: 213-23 |
| PMID | 23355257 |
| Title | 线粒体DNA (mtDNA) in brain samples from patients with major psychiatric disorders: gene expression profiles, mtDNA content and presence of the mtDNA common deletion. |
| Abstract | Several lines of evidence support a mitochondrial dysfunction in major psychiatric disorders. The objective of this study was to determine whether mitochondrial DNA (mtDNA) expression or content are implicated in the mitochondrial dysfunction observed inschizophrenia(SCH), bipolar disorder (BD), and major depressive disorder (MDD). MtDNA gene expression and mtDNA content (including the MT-ND4 deletion) were measured by RT-qPCR and qPCR, respectively. Post-mortem brain tissue from 60 subjects, divided evenly into four diagnostic groups (SCH, BD, MDD, and control (C)), was analyzed. MT-ND1gene expression was significantly increased in the BD group compared with the C group. MDD and SCH patients showed a similar pattern of mtDNA expression, which was different from that in BD patients. Similarly, a larger number of MDD and SCH patients tended to have the MT-ND4 gene deleted compared with BD and C subjects. However, no other significant differences were observed in mtDNA gene expression and mtDNA content. Notably, high variability was observed in the mtDNA gene expression and content in each diagnostic group. Previous studies and the present work provide evidence for a role of mtDNA in SCH, BD and MDD. However, further studies with larger patient and control groups as well as by analyzing distinct brain regions are needed to elucidate the role of mtDNA in major psychiatric disorders. |
| SCZ Keywords | schizophrenia |