Electron microscopy of oligodendroglia in severe mental illness

Na, Uranova; Orlovskaya, D.D.; Vikhreva, Olga; Zimina, I.S.; Kolomeets, Natalya S.; Vostrikov, V. M.; Rachmanova, V.I.

doi:10.1016/s0361-9230(01)00528-7

Cited by 451 publications

(312 citation statements)

References 51 publications

Supporting

Mentioning

284

Contrasting

Unclassified

Order By: Relevance

“…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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Specifically, two recent studies report decreased fiber number and density in the anterior commissure and the corpus callosum in women but not in men with schizophrenia (Highley et al, 1999a,b), and no differences in the number and density of fibers in the uncinate fasciculus (Highley et al, 2002). There is also growing evidence to suggest that glial cells, particularly oligodendrocytes, which form myelin sheaths around axons, are abnormal in schizophrenia (Hakak et al, 2001;Uranova et al, 2001Uranova et al, , 2004. For example, Hakak et al study reported abnormal expression of myelin related genes in schizophrenia, which suggests a disruption in oligodendrocyte function.…”

Section: Introductionmentioning

confidence: 99%

“…For example, Hakak et al study reported abnormal expression of myelin related genes in schizophrenia, which suggests a disruption in oligodendrocyte function. Furthermore, Uranova et al (2001) study, using electron microscopy, showed both qualitative and quantitative abnormalities in post-mortem brains of schizophrenics in the oligodentroglia in the prefrontal cortex and caudate nucleus, including a marked increase in the density of concentric lamellar bodies (indicating damage to myelinated fibers) in the caudate nucleus in post-mortem brains of patients diagnosed with schizophrenia, as well as decreased density of the oligodendrocytes in layer IV of the prefrontal cortex in schizophrenia (Uranova et al, 2004). In another study, Hof et al (2003) found decreased oligodendrocyte number and density in layer III of Brodmann area 9 and in gyral prefrontal white matter in schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

A review of diffusion tensor imaging studies in schizophrenia

Kubicki

McCarley

Westin

et al. 2007

Journal of Psychiatric Research

689

532

View full text Add to dashboard Cite

Both post-mortem and neuroimaging studies have contributed significantly to what we know about the brain and schizophrenia. MRI studies of volumetric reduction in several brain regions in schizophrenia have confirmed early speculations that the brain is disordered in schizophrenia. There is also a growing body of evidence suggesting that a disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, are responsible for the clinical symptoms and cognitive dysfunctions observed in this disorder. Thus an interest in white matter fiber tracts, subserving anatomical connections between distant, as well as proximal, brain regions, is emerging. This interest coincides with the recent advent of diffusion tensor imaging (DTI), which makes it possible to evaluate the organization and coherence of white matter fiber tracts. This is an important advance as conventional MRI techniques are insensitive to fiber tract direction and organization, and have not consistently demonstrated white matter abnormalities. DTI may, therefore, provide important new information about neural circuitry, and it is increasingly being used in neuroimaging studies of psychopathological disorders. Of note, in the past five years 18 DTI studies in schizophrenia have been published, most describing white matter abnormalities. Questions still remain, however, regarding what we are measuring that is abnormal in this disease, and how measures obtained using one method correspond to those obtained using other methods? Below we review the basic principles involved in MR-DTI, followed by a review of the different methods used to evaluate diffusion. Finally, we review MR-DTI findings in schizophrenia.

show abstract

“…[1][2][3] Multiple lines of evidence suggest that the integrity of myelin is disturbed in schizophrenia patients and that such abnormalities may be causally involved in the disease pathogenesis-for a comprehensive review see Davis et al 4 The three main lines of evidence are: (1) MRI and post-mortem studies show volume reductions and ultrastructural abnormalities in the white matter of the prefrontal cortex in schizophrenia patients. [5][6][7][8][9][10][11][12][13] (2) Gene expression profiling studies have demonstrated that several myelin-related genes are differentially expressed in post-mortem brain tissue of patients compared to unaffected controls. These genes include 2 0 -3 0 -cyclic nucleotide 3 0 -phosphodiesterase (CNP), V-ERB-B2 avian erythroblastic leukemia viral oncogene homologue 3 (ERBB3), gelsolin (GSN), myelin and lymphocyte protein (MAL), myelin-associated glycoprotein (MAG), myelin and lymphocyte protein (MLP) and transferin (TF).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2007

View full text Add to dashboard Cite

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.

show abstract

Electron microscopy of oligodendroglia in severe mental illness

Cited by 451 publications

References 51 publications

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

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

A review of diffusion tensor imaging studies in schizophrenia

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

Contact Info

Product

Resources

About