Deficit of perineuronal oligodendrocytes in the prefrontal cortex in schizophrenia and mood disorders

Vostrikov, V. M.; Na, Uranova; Orlovskaya, D.D.

doi:10.1016/j.schres.2007.04.014

Cited by 210 publications

(167 citation statements)

References 70 publications

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“…The cytoarchitectural traits related to oligodendrocytes that were used in this study were originally reported by Dr Natalya Uranova and colleagues. 4,5 They identified a significant reduction of perineuronal oligodendrocytes in layer III of BA9 5 in all three psychiatric disorders as well as a decrease in the density of oligodendrocytes in layer VI of BA9. 4 Our correlation analysis revealed that 818 genes were significantly associated with the number of perineuronal oligodendrocytes in the frontal cortex of all subjects in the SNC (Supplementary Table 1).…”

Section: Discussionmentioning

confidence: 98%

“…3 Neuropathological studies have revealed reduced density of oligodendrocytes, 4 reduced numbers of oligodendrocytes associated with a pyramidal neuron, 5 decreased cell size of pyramidal neurons 5 and reduced cell density of g-aminobutyric acid (GABA)ergic interneurons 6 in the PFC. Although neurodevelopmental deficits and apoptosis may contribute to these cytoarchitectural abnormalities, the molecular mechanisms that underlie them remain to be determined.…”

Section: Introductionmentioning

confidence: 99%

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Correlation analysis between genome-wide expression profiles and cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders

2008

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Cytoarchitectural abnormalities have been described in the prefrontal cortex of subjects with schizophrenia, bipolar disorder and depression. However, little is known about the gene expression profiles associated with these abnormalities. Genome-wide expression profiling technology provides an unbiased approach to identifying candidate genes and biological processes that may be associated with complex biological traits such as cytoarchitecture. In this study, we explored expression profiles associated with the abnormalities by using publicly available microarray metadata and cytoarchitectural data from post-mortem samples of the frontal cortex from 54 subjects (schizophrenia, n = 14; bipolar disorder, n = 13; depression, n = 12 and controls n = 15). Correlation analysis between genome-wide expression levels and cytoarchitectural traits revealed that 818 genes were significantly correlated with a decrease in the number of perineuronal oligodendrocytes across all subjects. A total of 600 genes were significantly correlated with a decrease in density of calbindin-positive interneurons across all subjects. Multiple biological processes including cellular metabolism, central nervous system development, cell motility and programmed cell death were significantly overrepresented in both correlated gene lists. These findings may provide novel insights into the molecular mechanisms that underlie the cytoarchitectural abnormalities of perineuronal oligodendrocytes and calbindin-containing GABAergic interneurons in the prefrontal cortex of the major psychiatric disorders.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Correlation analysis between genome-wide expression profiles and cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders

2008

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“…1 Ten paraffin sections per case of PFC (BA9) were used for counting the number of perineuronal oligodendrocytes. 2 Oligodendrocytes located within a distance of 5 mm from a neuron were counted after Nissl staining. Oligodendrocytes were identified by their characteristic morphology, including a small round or oval nucleus with relatively dense nuclear staining and a narrow unstained rim of the cytoplasm.…”

Section: Cytoarchitectural Traitsmentioning

confidence: 99%

“…Oligodendrocytes were identified by their characteristic morphology, including a small round or oval nucleus with relatively dense nuclear staining and a narrow unstained rim of the cytoplasm. 2 The genome-wide association analyses for the cytoarchitectural traits were performed using a multiple linear regression model with covariates. A correlation test was conducted to examine the association between the clinical variables-age of onset and antipsychotic treatment-and the traits (StatView, SAS, Cary, NC, USA).…”

Section: Cytoarchitectural Traitsmentioning

confidence: 99%

“…Reduced density of calbindin-containing g-aminobutyric acid (GABA)ergic interneurons 1 and reduced numbers of oligodendrocytes associated with a pyramidal neuron 2 have been described in the prefrontal cortex (PFC) of the major psychiatric disorders, schizophrenia, bipolar disorder, and depression. In a previous study, we identified potential molecular mechanisms that may underlie these abnormalities using correlation analyses between genome-wide expression profiles and the cytoarchitectural traits.…”

Section: Introductionmentioning

confidence: 99%

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Integrative genome-wide association analysis of cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders

Kim

Webster

2010

Mol Psychiatry

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Cytoarchitectural abnormalities have been described in the prefrontal cortex (PFC) of subjects with psychiatric disorders. We explored the possible genetic causalities that may underlie the cytoarchitectural abnormalities of calbindin-containing c-aminobutyric acid (GABA)ergic neurons and perineuronal oligodendrocytes in the PFC of subjects with psychiatric disorders by converging results from genome-wide single-nucleotide polymorphism (SNP) scans for the traits and expression SNP (eSNP) associations. In the initial genome-wide scans, we identified several development-and apoptosis-related genes associated with the cytoarchitectural traits. Moreover, the susceptibility gene for bipolar disorder, PPP2R2C, was found to be associated with the number of perineuronal oligodendrocytes. Further eSNP analyses indicated that two novel candidate genes, RAB2A and SLC38A1, were associated with the density of calbindinpositive neurons and the number of perineuronal oligodendrocytes, respectively. Our findings may provide novel insights into the genetic causalities associated with cytoarchitectural abnormalities in the PFC of subjects with major psychiatric disorders as well as into the etiology of such disorders.

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Influence of Genes and Environment on Brain Volumes in Twin Pairs Concordant and Discordant for Bipolar Disorder

Schot¹,

Vonk²,

Brans³

et al. 2009

Arch Gen Psychiatry

103

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Deficit of perineuronal oligodendrocytes in the prefrontal cortex in schizophrenia and mood disorders

Cited by 210 publications

References 70 publications

Correlation analysis between genome-wide expression profiles and cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders

Correlation analysis between genome-wide expression profiles and cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders

Integrative genome-wide association analysis of cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders

Influence of Genes and Environment on Brain Volumes in Twin Pairs Concordant and Discordant for Bipolar Disorder

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