Abstract
Microglial activation has been proposed to be involved in the pathophysiology of schizophrenia (SCZ). We hypothesized that dystrophic alterations of oligodendrocytes previously reported in the prefrontal white matter in SCZ might be associated with microglial activation in the acute state of SCZ. White matter of the prefrontal cortex (BA10) was studied in post-mortem brain tissue from 21 SCZ cases and 20 normal controls. The SCZ group included 12 subjects with predominantly positive symptoms and 9 subjects with predominantly negative symptoms. Electron microscopy was applied to estimate cell density, size, volume fraction (Vv) and the number (N) of organelles in oligodendrocytes adjacent to microglia and in oligodendrocytes adjacent to myelin, neurons and capillaries and not adjacent to microglia. Cell density of oligodendrocytes was not changed in the SCZ group as compared to controls. Vv and N of mitochondria were significantly decreased, while Vv of vacuoles of endoplasmic reticulum and lipofuscin granules were significantly increased in oligodendrocytes adjacent to either microglia or myelin in the SCZ group and in patients displaying predominantly positive symptoms as compared to the control group. There were no significant differences between oligodendrocytes adjacent to microglia and to myelin. Vv and N of lipofuscin were also increased in peri-capillary oligodendrocytes. There was no effect of clinical subgroups on the parameters of peri-capillary and peri-neuronal oligodendrocytes. Though many ameboid and dystrophic microglia adjacent to oligodendrocytes were found in the SCZ samples, we provide no quantitative evidence that oligodendrocyte dystrophy is associated with microglial activation in white matter in SCZ.
Highlights
Neuroimaging studies of patients with schizophrenia (SCZ) have provided evidence for dysconnectivity between different brain areas and a widespread disruption of white matter (WM) integrity associated with both negative and positive symptoms, as well as with cognitive disturbances.[1]
The rod-like microglial cells were often present in both control and SCZ samples
We found an effect of age of onset of disease on Vv of mitochondria: [F(2.37) = 3.73, p = 0.03] and N of mitochondria [F (2. 37) = 3.36, p = 0.04] in oligodendrocytes adjacent to microglia (ANCOVA)
Summary
Neuroimaging studies of patients with schizophrenia (SCZ) have provided evidence for dysconnectivity between different brain areas and a widespread disruption of white matter (WM) integrity associated with both negative and positive symptoms, as well as with cognitive disturbances.[1]. Immunoreactive oligodendrocytes in fronto-parietal WM of patients with paranoid SCZ as compared to controls and undifferentiated/residual SCZ. Oligodendrocytes are often located adjacent to microglial cells in gray and WM in both control and SCZ cases. Qualitative ultrastructural analysis from an electron microscopic study revealed “activated” microglia, containing invaginated nuclei and vacuolated cytoplasm, adjacent to dystrophic oligodendroglia in the prefrontal WM11–13 and hippocampus[14] of subjects with SCZ as compared to normal controls. These data suggest that microglial activation might be involved in oligodendrocyte abnormalities in SCZ
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