Ultrastructural pathology of oligodendrocytes adjacent to microglia in prefrontal white matter in schizophrenia

Uranova, N.A.; Vikhreva, Olga; Rakhmanova, V. I.; Orlovskaya, D.D.

doi:10.1038/s41537-018-0068-2

Cited by 35 publications

(45 citation statements)

References 43 publications

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“…Taken together, these data suggest that altered relationships between microglia and oligodendrocytes are associated with chronic schizophrenia and with deleterious effect of the disturbed metabolism in microglia on the oligodendrocyte metabolism in the SPPS subgroup in acute stage of disease, during relapse. Similar alterations of oligodendrocytes adjacent to microglia have been previously reported in the prefrontal white matter in chronic schizophrenia cases (21). We found significant positive correlations between Vv and N of mitochondria in microglia and Vv and N of mitochondria in oligodendrocytes only in the SPPS subgroup.…”

Section: Discussionsupporting

confidence: 90%

“…The mechanisms of oligodendrocyte and myelin abnormalities in schizophrenia remain uncertain. Oligodendrocytes are often located adjacent to microglial cells in both control and schizophrenia (21). Previously we found dystrophic alterations in oligodendrocytes adjacent to microglia and myelin in the prefrontal white matter in the schizophrenia patients with predominantly positive symptoms as compared to controls (21).…”

Section: Introductionmentioning

confidence: 72%

“…Also chlorpromazine equivalents were estimated for the patient's last 30 days. Causes of death were the same in the control and the schizophrenia groups [see (21)].…”

Section: Subjectsmentioning

confidence: 99%

“…Tissue preparation was described in details in our previous paper (21). Sections were viewed with a JEM-100B (JEOL, Japan) electron microscope.…”

Section: Tissue Preparationmentioning

confidence: 99%

“…Areas of cells and cellular organelles were estimated using test grids for two-dimensional counts, superimposed on the negatives at the final magnification *26,000. The counting method was previously described in details (21).…”

Section: Morphometrymentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 72%

“…Also chlorpromazine equivalents were estimated for the patient's last 30 days. Causes of death were the same in the control and the schizophrenia groups [see (21)].…”

Section: Subjectsmentioning

confidence: 99%

“…Tissue preparation was described in details in our previous paper (21). Sections were viewed with a JEM-100B (JEOL, Japan) electron microscope.…”

Section: Tissue Preparationmentioning

confidence: 99%

Section: Morphometrymentioning

confidence: 99%

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