Microarray analysis of postmortem temporal cortex from patients with schizophrenia

Aston, Christopher E.; Jiang, Lixin; Sokolov, Boris P.

doi:10.1002/jnr.20208

Cited by 263 publications

(196 citation statements)

References 38 publications

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“…Furthermore, the circadian pattern of FBXL21 expression in the mouse suprachiasmatic nucleus (region responsible for controlling circadian rhythm) is reminiscent of the expression pattern seen for other circadian pacemaker genes such as Period 1 (PER1) (Dardente et al, 2008). Mutations in either the FBXL21 or FBXL3 genes can lead to a dysfunction of circadian rhythm oscillations and lead to significant behavioral disturbances in individuals and alterations in their sleeping patterns; moreover the absence of FBXL21 causes a short-period phenotype in both mice and cells (Hirano et al, 2013;Yoo et al, 2013 (Bromundt et al, 2011); which is further supported by a microarray study which found a significant downregulation of the circadian pacemaker gene PER1 in the postmortem temporal cortex of schizophrenia patients compared to healthy controls (Aston et al, 2004). Furthermore, an animal model study has shown dysfunction in the synchronization of circadian rhythms between brain cell networks involved in sleep-wake regulation and cognition (Dudley et al, 2003).…”

Section: Discussionmentioning

confidence: 77%

Investigation of genetic variants in ubiquitin enzyme genes involved in the modulation of neurodevelopmental processes: a role in schizophrenia susceptibility?

Andrews

Fernandez

2014

Genet. Res.

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Despite extensive research during the last few decades, the etiology of schizophrenia remains unclear. Evidence of both genetic and environmental influences in the developmental profile of schizophrenia has grown, and due to the complexity of this disorder, a polygenic aspect has been associated with this neuropsychiatric pathology. Unfortunately, no diagnostic strategies based on biological measurement or genetic testing is currently available for schizophrenia. Gene-expression profiling and recent protein studies have shown a decrease in the expression of ubiquitin pathway proteins in the prefrontal cortex of schizophrenia patients. We have examined single nucleotide polymorphisms (or SNPs) within three genes from the ubiquitin protein system: the ubiquitin conjugating enzyme E2D1 (UBE2D1) gene, the E3 SUMOprotein ligase protein inhibitor of activated STAT 2 (PIAS2) gene, and the E3 ubiquitin ligase F-box and leucine-rich repeat protein 21 (FBXL21) gene, in a Caucasian case-control population for schizophrenia. After Bonferroni correction for multiple testing was applied, no significant associations were reported for any of the tested SNPs. Additional genetic analyses will be necessary to fully explore the role of these three genes in schizophrenia. Regarding the rising interest in ubiquitin-related proteins as a therapeutic target in other pathologies such as cancer, further research into the role of ubiquitin pathways in schizophrenia seems topical and timely. SummaryDespite extensive research during the last decades, the etiology of schizophrenia remains unclear. Evidence of both genetic and environmental influences in the developmental profile of schizophrenia has grown, and due to the complexity of this disorder, a polygenic aspect has been associated with this neuropsychiatric pathology. Unfortunately, no diagnostic strategies based on biological measurement or genetic testing is currently available for schizophrenia. Gene expression profiling and recent protein studies have shown a decrease in the expression of ubiquitin pathway proteins in the prefrontal cortex of schizophrenia patients. We have examined Single Nucleotide Polymorphisms (or SNPs) within three genes from the ubiquitin protein system: the ubiquitin conjugating enzyme E2D1 (UBE2D1) gene, the E3 SUMO-protein ligase protein inhibitor of activated STAT 2 (PIAS2) gene, and the E3 ubiquitin ligase F-box and leucine-rich repeat protein 21 (FBXL21) gene, in a Caucasian case-control population for schizophrenia. After Bonferroni correction for multiple testing was applied, no significant associations were reported for any of the tested SNPs. Additional genetic analyses will be necessary to fully explore the role of these three genes in schizophrenia. Regarding the rising interest of ubiquitin related proteins as a therapeutic target in other pathologies such as cancer, further research into the role of ubiquitin pathways in schizophrenia seem topical and timely.

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Section: Discussionmentioning

confidence: 77%

Investigation of genetic variants in ubiquitin enzyme genes involved in the modulation of neurodevelopmental processes: a role in schizophrenia susceptibility?

Andrews

Fernandez

2014

Genet. Res.

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“…36,37,58,59 Few studies have explored global expression changes between groups of suicides and psychiatrically normal controls, some have however focused on a particular psychiatric diagnosis, such as bipolar disorder or schizophrenia, and included within these groups subjects that died by suicide. [60][61][62][63][64][65][66][67] Sibille et al 51 recently compared expression patterns in BA9 and BA47 of depressed suicides versus psychiatrically normal controls matched on the basis of sex, age, DAVID genes correspond to the total number of unique DAVID annotated genes. The percentage represents the number of differentially expressed genes belonging to a given category over the total number of DAVID annotated genes.…”

Section: Discussionmentioning

confidence: 99%

Patterns of gene expression in the limbic system of suicides with and without major depression

et al. 2007

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The limbic system has consistently been associated with the control of emotions and with mood disorders. The goal of this study was to identify new molecular targets associated with suicide and with major depression using oligonucleotide microarrays in the limbic system (amygdala, hippocampus, anterior cingulate gryus (BA24) and posterior cingulate gyrus (BA29)). A total of 39 subjects were included in this study. They were all male subjects and comprised 26 suicides (depressed suicides = 18, non depressed suicides = 8) and 13 matched controls. Brain gene expression analysis was carried out on human brain samples using the Affymetrix HG U133 chip set. Differential expression in each of the limbic regions showed group-specific patterns of expression, supporting particular neurobiological mechanisms implicated in suicide and depression. Confirmation of genes selected based on their significance and the interest of their function with reverse transcriptase-polymerase chain reaction showed consistently correlated signals with the results obtained in the microarray analysis. Gene ontology analysis with differentially expressed genes revealed an overrepresentation of transcription and metabolism-related genes in the hippocampus and amygdala, whereas differentially expressed genes in BA24 and BA29 were more generally related to RNA-binding, regulation of enzymatic activity and protein metabolism. Limbic expression patterns were most extensively altered in the hippocampus, where processes related to major depression were associated with altered expression of factors involved with transcription and cellular metabolism. Additionally, our results confirm previous evidence pointing to global alteration of gabaergic neurotransmission in suicide and major depression, offering new avenues in the study and possibly treatment of such complex disorders. Overall, these data suggest that specific patterns of expression in the limbic system contribute to the etiology of depression and suicidal behaviors and highlight the role of the hippocampus in major depression.

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“…Increased or decreased expression of PLP1 as a result of point-mutations or duplications of the PLP1 gene cause dysmyelination of axon tracts and has been associated with pathologies such as Pelizaeus-Merzbacher disease (PMD) and X-linked spastic paraplegia type 2 (SPG2) [35,52,54]. In addition, expression of the PLP1 transcript was reported decreased in temporal cortex in schizophrenia [55]. The severity of the mutant PLP1 phenotypes has been studied extensively in human postmortem brain as well as in rodent experimental models.…”

Section: Discussionmentioning

confidence: 99%

Expression of Transcripts for Myelin Related Genes in Postmortem Brain from Cocaine Abusers

2008

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Chronic abuse of cocaine is known to cause neuroadaptive changes in the nucleus accumbens (NAc) and ventral tegmental area (VTA). In addition, altered expression of the myelin-related genes MBP, MOBP, PLP1 as well as of MAL2 in NAc was recently reported by gene array analysis in brains from cocaine abusers. In the present study we used in situ hybridization to quantify transcript expression of these four genes, as well as for the myelin-related transcripts encoding quaking, EDG2, claudin-11, transferrin, CNP, and MAG in caudate, putamen, internal capsule, and NAc in postmortem brain from cocaine abusers and matched comparison subjects. Most transcripts were not different between these groups in these striatal regions, and contrary to previous reports, we did not detect any changes in the NAc. However, expression of the transcript encoding PLP1 was significantly decreased in ventral and dorsal regions of the caudate, putamen, and in the internal capsule. Additionally, expression of claudin-11 and transferrin was decreased in the caudate and internal capsule, respectively. PLP1 is expressed at very high levels in oligodendrocytes and is essential in maintaining stability of myelin sheets. Based on these findings, altered expression of PLP1 in most areas of the striatum suggests that widespread changes to the myelin structure could be associated with the adaptive changes following chronic cocaine abuse.

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Microarray analysis of postmortem temporal cortex from patients with schizophrenia

Cited by 263 publications

References 38 publications

Investigation of genetic variants in ubiquitin enzyme genes involved in the modulation of neurodevelopmental processes: a role in schizophrenia susceptibility?

Investigation of genetic variants in ubiquitin enzyme genes involved in the modulation of neurodevelopmental processes: a role in schizophrenia susceptibility?

Patterns of gene expression in the limbic system of suicides with and without major depression

Expression of Transcripts for Myelin Related Genes in Postmortem Brain from Cocaine Abusers

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