Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the Stanley Neuropathology Consortium

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

doi:10.1016/s0920-9964(03)00181-6

Cited by 593 publications

(433 citation statements)

References 35 publications

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“…As stress is associated with the risk of developing depression (Kessler, 1997;Kendler et al, 1999), the morphological findings of preclinical studies, where animals are exposed to chronic stressful experiences, are commonly related to the structural changes reported in the brains of depressed patients. In vivo imaging studies reveal selective volume reduction in the PFC (Drevets, 2000), and post mortem histological data show reductions in neuronal size and glial cell numbers in specific subregions of the frontal cortex in depressed patients (Ö ngür et al, 1998;Rajkowska et al, 1999;Cotter et al, 2001aCotter et al, , 2002Uranova et al, 2004). It is tempting to speculate that our finding on the pronounced changes in gliogenesis after chronic stress exposure may relate to the abnormalities of glial cell numbers reported in the frontolimbic areas of depressed patients.…”

Section: Stress-induced Structural Changes and Their Potential Implicmentioning

confidence: 75%

Chronic Social Stress Inhibits Cell Proliferation in the Adult Medial Prefrontal Cortex: Hemispheric Asymmetry and Reversal by Fluoxetine Treatment

Czéh

Müller-Keuker

Ryguła

et al. 2006

Neuropsychopharmacol

316

221

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Profound neuroplastic changes have been demonstrated in various limbic structures after chronic stress exposure and antidepressant treatment in animal models of mood disorders. Here, we examined in rats the effect of chronic social stress and concomitant antidepressant treatment on cell proliferation in the medial prefrontal cortex (mPFC). We also examined possible hemispheric differences. Animals were subjected to 5 weeks of daily social defeat by an aggressive conspecific and received concomitant, daily, oral fluoxetine (10 mg/kg) during the last 4 weeks. Bromodeoxyuridine (BrdU) labeling and quantitative stereological techniques were used to evaluate the treatment effects on proliferation and survival of newborn cells in limbic structures such as the mPFC and the hippocampal dentate gyrus, in comparison with nonlimbic structures such as the primary motor cortex and the subventricular zone. Phenotypic analysis showed that neurogenesis dominated the dentate gyrus, whereas in the mPFC most newborn cells were glia, with smaller numbers of endothelial cells. Chronic stress significantly suppressed cytogenesis in the mPFC and neurogenesis in the dentate gyrus, but had minor effect in nonlimbic structures. Fluoxetine treatment counteracted the inhibitory effect of stress. Hemispheric comparison revealed that the rate of cytogenesis was significantly higher in the left mPFC of control animals, whereas stress inverted this asymmetry, yielding a significantly higher incidence of newborn cells in the right mPFC. Fluoxetine treatment abolished hemispheric asymmetry in both control and stressed animals. These pronounced changes in gliogenesis after chronic stress exposure may relate to the abnormalities of glial cell numbers reported in the frontolimbic areas of depressed patients.

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Section: Stress-induced Structural Changes and Their Potential Implicmentioning

confidence: 75%

Chronic Social Stress Inhibits Cell Proliferation in the Adult Medial Prefrontal Cortex: Hemispheric Asymmetry and Reversal by Fluoxetine Treatment

Czéh

Müller-Keuker

Ryguła

et al. 2006

Neuropsychopharmacol

316

221

View full text Add to dashboard Cite

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“…Postmortem examination of schizophrenic brains has demonstrated structural abnormalities in both myelin sheaths and oligodendroglia and it has been hypothesized that oligodendroglial dysfunction induces abnormalities in myelin, thereby contributing to the disease etiology. [46][47][48] Alternatively, aberrant PI levels may influence vesicle trafficking and vesicle cycling, important determinants in neurotransmitter cycling. Hence, PI kinase genes (including PIK4CA, PIP5K2A and PIK3C2G) are functional candidates for contributing to the risk of developing schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

An association screen of myelin-related genes implicates the chromosome 22q11 PIK4CA gene in schizophrenia

et al. 2007

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Several lines of evidence, including expression analyses, brain imaging and genetic studies suggest that the integrity of myelin is disturbed in schizophrenia patients. In this study, we first reconstructed a pathway of 138 myelin-related genes, all involved in myelin structure, composition, development or maintenance. Then we performed a two-stage association analysis on these 138 genes using 771 single nucleotide polymorphisms (SNPs). Analysis of our data from 310 cases vs 880 controls demonstrated association of 10 SNPs from six genes. Specifically, we observed highly significant P-values for association in PIK4CA (observed P = 6.1 Â 10 À6 ). These findings remained significant after Bonferroni correction for 771 tests. The PIK4CA gene is located in the chromosome 22q11 deletion syndrome region, which is of particular interest because it has been implicated in schizophrenia. We also report weak association of SNPs in PIK3C2G, FGF1, FGFR1, ARHGEF10 and PSAP (observed Pp0.01). Our approach-of screening genes involved in a particular pathway for association-resulted in identification of several, mostly novel, genes associated with the risk of developing schizophrenia in the Dutch population.

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“…33,[72][73][74][75] Moreover, several studies have evidence for deficits in oligodendrocytes in the disorder. [76][77][78][79] These oligodendrocyte abnormalities may in turn contribute to the loss of coherence of axon tracts, and reduced connectivity, in schizophrenia. 80,81 Alterations in NRG1-ERBB4 and/or PTPRZ1 signaling may cause these oligodendrocyte abnormalities, in addition to potential neuronal effects.…”

Section: Discussionmentioning

confidence: 99%

Molecular dissection of NRG1-ERBB4 signaling implicates PTPRZ1 as a potential schizophrenia susceptibility gene

et al. 2007

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Neuregulin and the neuregulin receptor ERBB4 have been genetically and functionally implicated in schizophrenia. In this study, we used the yeast two-hybrid system to identify proteins that interact with ERBB4, to identify genes and pathways that might contribute to schizophrenia susceptibility. We identified the MAGI scaffolding proteins as ERBB4-binding proteins. After validating the interaction of MAGI proteins with ERBB4 in mammalian cells, we demonstrated that ERBB4 expression, alone or in combination with ERBB2 or ERBB3, led to the tyrosine phosphorylation of MAGI proteins, and that this could be further enhanced with receptor activation by neuregulin. As MAGI proteins were previously shown to interact with receptor phosphotyrosine phosphatase b/f (RPTPb), we postulated that simultaneous binding of MAGI proteins to RPTPb and ERBB4 forms a phosphotyrosine kinase/phosphotyrosine phosphatase complex. Studies in cultured cells confirmed both a spatial and functional association between ERBB4, MAGI and RPTPb. Given the evidence for this functional association, we examined the genes coding for MAGI and RPTPb for genetic association with schizophrenia in a Caucasian United Kingdom case-control cohort (n = B1400). PTPRZ1, which codes for RPTPb, showed significant, gene-wide and hypothesis-wide association with schizophrenia in our study (best individual single-nucleotide polymorphism allelic P = 0.0003; gene-wide P = 0.0064; hypothesiswide P = 0.026). The data provide evidence for a role of PTPRZ1, and for RPTPb signaling abnormalities, in the etiology of schizophrenia. Furthermore, the data indicate a role for RPTPb in the modulation of ERBB4 signaling that may in turn provide further support for an important role of neuregulin/ERBB4 signaling in the molecular basis of schizophrenia.

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Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the Stanley Neuropathology Consortium

Cited by 593 publications

References 35 publications

Chronic Social Stress Inhibits Cell Proliferation in the Adult Medial Prefrontal Cortex: Hemispheric Asymmetry and Reversal by Fluoxetine Treatment

Chronic Social Stress Inhibits Cell Proliferation in the Adult Medial Prefrontal Cortex: Hemispheric Asymmetry and Reversal by Fluoxetine Treatment

An association screen of myelin-related genes implicates the chromosome 22q11 PIK4CA gene in schizophrenia

Molecular dissection of NRG1-ERBB4 signaling implicates PTPRZ1 as a potential schizophrenia susceptibility gene

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