Reduced oligodendrocyte density in layer 5 of the prefrontal cortex in schizophrenia

Kolomeets, Natalya S.; Uranova, N.A.

doi:10.1007/s00406-018-0888-0

Cited by 50 publications

(29 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recently we have reported reduced oligodendrocyte density (-32%) in layer 5 of the PFC (Brodmann's area 10) in schizophrenia (12). In the present study we found dystrophic changes but no degeneration of oligodendrocytes in layer 5 of the PFC in schizophrenia.…”

Section: Discussionsupporting

confidence: 61%

“…These data suggest that neuroinflammation might be present in different subgroups of schizophrenia patients. Previously we found lowered oligodendrocyte density in layer 5 of the PFC in the schizophrenia patients (12). We hypothesized that oligodendrocyte dystrophy may be at least in part associated with increased activation of microglial cells located adjacent to dystrophic oligodendrocytes in the schizophrenia patients during acute psychosis.…”

Section: Introductionmentioning

confidence: 85%

“…Pathology of oligodendrocytes and myelin is considered to be a biological basis for dysconnectivity in schizophrenia (2,8). Reduced oligodendrocyte density (9)(10)(11)(12), ultrastructural alterations of oligodendrocytes and myelinated fibers (13)(14)(15), altered intracortical myelin staining (16) and impaired differentiation of oligodendrocyte precursors (17) have been reported in the PFC in schizophrenia. Abnormalities of myelination, reduced expression and dysregulation of oligodendrocyte and myelin-related genes (18)(19)(20) have been detected in the PFC in schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dystrophy of Oligodendrocytes and Adjacent Microglia in Prefrontal Gray Matter in Schizophrenia

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background: Some evidence support the notion that microglia activation in acute state of schizophrenia might contribute to damage of oligodendrocytes and myelinated fibers. Previously we found dystrophic changes of oligodendrocytes in prefrontal white matter in schizophrenia subjects displaying predominantly positive symptoms as compared to controls. The aim of the study was to verify whether microglial activation might contribute to dystrophic changes of oligodendrocytes in prefrontal gray matter in this clinical subgroup. Methods: Transmission electron microscopy and morphometry of microglia and adjacent oligodendrocytes were performed in layer 5 of the prefrontal cortex (BA10) in the schizophrenia subjects displaying predominantly positive symptoms (SPPS, n = 12), predominantly negative symptoms (SPNS, n = 9) and healthy controls (n = 20). Results: Qualitative study showed microglial activation and dystrophic alterations of microglia and oligodendrocytes adjacent to each other in both subgroups as compared to controls. A significant reduction in volume density (Vv) and the number (N) of mitochondria and an increase in N of lipofuscin granules were found in oligodendrocytes and adjacent microglia in both subgroups. Vv of lipofuscin granules, Vv and N of vacuoles of endoplasmic reticulum in microglia were increased significantly in the SPPS subgroup as compared to controls. In the SPPS subgroup Vv and N of mitochondria in microglia were correlated with N of vacuoles in microglia (r =-0.61, p < 0.05) and with Vv (r = 0.79, p < 0.01) and N (r = 0.59, p < 0.05) of mitochondria in oligodendrocytes. Vv of mitochondria in microglia was also correlated with Vv and N of vacuoles in oligodendrocytes in the SPPS subgroup (r = 0.76, p < 0.01). Area of nucleus of microglial cells was correlated negatively with age (r =-0.76, p < 0.01) and age at illness onset (r =-0.65, p < 0.05) in the SPPS subgroup. In the SPNS subgroup N of mitochondria in microglia was correlated with Vv of lipofuscin granules in oligodendrocytes (r =-0.9, p < 0.01). There were no significant correlations between these parameters in the control group. Discussion: Microglial dystrophy might contribute to oligodendrocyte dystrophy in the schizophrenia subjects with predominantly positive symptoms during relapse. Mitochondria in microglia and oligodendrocytes may be a target for treatment strategy of schizophrenia.

show abstract

Section: Discussionsupporting

confidence: 61%

Section: Introductionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dystrophy of Oligodendrocytes and Adjacent Microglia in Prefrontal Gray Matter in Schizophrenia

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Myelin structure that consists of the multi-lamella layer of plasma membranes formed by one of glia cells, oligodendrocyte, acts as the electrical insulator to control the saltatory conduction. A number of studies have demonstrated that myelin formation is also required for neuronal integrity, so that the defects of these structures cause neuronal and mental diseases, such as multiple sclerosis (MS) 4-8 , leukoencephalopathy 9 , and schizophrenia [10][11][12] . Pathological characteristics of some of these disorders in the spinal cord show that small diameter axons are more vulnerable, compared with large diameter axons 4,7 .…”

Section: Development Of Type I/ii Oligodendrocytes Regulated By Teneumentioning

confidence: 99%

Development of type I/II oligodendrocytes regulated by teneurin-4 in the murine spinal cord

Hayashi

Suzuki

Takahashi

et al. 2020

Sci Rep

View full text Add to dashboard Cite

PBS, were incubated overnight at 4 °C. After washing with PBS for 3 times, the sections were labeled with secondary antibodies, rabbit IgG-Alexa 488 (ThermoFisher Scientific), rabbit IgG-Alexa 594 (ThermoFisher Scientific), mouse IgG-Alexa 488 (ThermoFisher Scientific) and mouse IgG-Alexa 594 (ThermoFisher Scientific) for 50 min at room temperature. After 3 times washing with PBS, the samples were mounted with Vectashield containing DAPI (Vector Laboratories). The fluorescent images were taken and analyzed by the fluorescence microscope BZ-X700 (Keyence) or the confocal microscope LSM 700 ZEN (Zeiss). In all immunohistochemical analyses, triplicate or quadruplicate independent experiments gave similar results. Also, the specificity of anti-CAII and other cell-type marker antibodies was validated (Supplementary Fig. S5). Electron microscopy analysis. The spinal cords of P7 pups were dissected out and fixed with 2% PFA, 2% glutaraldehyde, and 2.5% sucrose in 0.1 M cacodylate buffer, including 2% osmium tetroxide, for 3 h at 4 °C. After fixation, the tissues were washed with 0.1 M cacodylate buffer 3 times. The following procedures of transmission electron microscopy analysis were performed by Tokai Electron Microscopy Analysis Co., Ltd. Statistical analyses. All of the experiments were independently performed at least 3 times. The two-tailed Student's t-test was used for the analyses in the experiments with two groups. One-way ANOVA followed by Tukey's post hoc test was used for the statistical analysis for multiple comparisons. The statistical significance was defined as *p < 0.05, **p < 0.01, and ***p < 0.001.

show abstract

“…In the entorhinal cortex of schizophrenia patients, we detected a decreased intensity of myelin basic protein (MBP) staining and found that decreased myelination correlated with disorganization of pre-alpha cells [3], demonstrating that disturbed neurodevelopment in these disorders might be the basis of disturbed myelin-based connectivity. In the gray matter of the prefrontal cortex, Kolomeets and Uranova report a reduction of the density of oligodendrocytes in schizophrenia [4]. Moreover, previous electron microscopy studies from that group in cases with very low postmortem intervals (time from death to autopsy) provided evidence for damaged myelin sheaths, myelin degeneration, and apoptosis/necrosis of oligodendrocytes in gray and white matter of the prefrontal cortex of patients with schizophrenia and affective disorders.…”

mentioning

confidence: 91%

A new role for oligodendrocytes and myelination in schizophrenia and affective disorders?

Schmitt

Simons

Cantuti-Castelvetri

et al. 2019

Eur Arch Psychiatry Clin Neurosci

View full text Add to dashboard Cite

Reduced oligodendrocyte density in layer 5 of the prefrontal cortex in schizophrenia

Cited by 50 publications

References 67 publications

Dystrophy of Oligodendrocytes and Adjacent Microglia in Prefrontal Gray Matter in Schizophrenia

Dystrophy of Oligodendrocytes and Adjacent Microglia in Prefrontal Gray Matter in Schizophrenia

Development of type I/II oligodendrocytes regulated by teneurin-4 in the murine spinal cord

A new role for oligodendrocytes and myelination in schizophrenia and affective disorders?

Contact Info

Product

Resources

About