[Specific interactions between microglia and oligodendrocytes in white matter in continuous schizophrenia]
N A Uranova1, O V Vikhreva1, V I Rakhmanova1
1Mental Health Research Center, Moscow, Russia.
Objective:
To study the ultrastructure of microglia adjacent to oligodendrocytes in white matter of the prefrontal cortex in continuous schizophrenia (CSch) as compared to controls and attack-like schizophrenia (ASch) and to perform correlation analysis between the parameters of microglia and adjacent oligodendrocytes previously detected in both clinical types of schizophrenia.
Material And Methods:
Electron microscopic morphometric study of microglia adjacent to oligodendrocytes was performed in postmortem white matter of the prefrontal cortex (BA10) in 9 cases of CSch, 8 cases of ASch and 20 healthy controls. Group comparisons were made by ANCOVA and Pearson correlation analyses.
Results:
The reduction of volume fraction (Vv) and the number of mitochondria in microglia was found in elderly subjects (>50 y.o.) as compared to young controls (60%, p<0.05), and the increase in these parameters of lipofuscin granules were detected in elderly subjects as compared to elderly controls in CSch (470%, 606%, p<0.001). Vv and the number of mitochondria in microglia correlated negatively with area of heterochromatin in microglia (r≥-0.7, p<0.05), and area of lipofuscin correlated positively with area of heterochromatin in microglia (r=0.76, p<0.05) and with illness duration (r=0.7, p<0.05) only in the CSch group. The numerical density of microglia was not changed in both schizophrenia groups. Area of heterochromatin was increased in both groups as compared to controls (p<0.05) and correlated negatively with the numerical density of microglia in the CSch group. The number of mitochondria in oligodendrocytes (reduced in CSch) correlated positively with the number of mitochondria in microglia and negatively with Vv of lipofuscin granules in microglia and with area of microglial nucleus only in the CSch group.
Conclusion:
Specific features of CSch as compared to ASch might be associated with the disturbances of mitochondrial and lipid metabolism in microglia, dysfunction of nucleus and accelerated aging of microglia that might lead to alterations of mitochondrial metabolism in oligodendrocytes.
Insights
Schizophrenia (CSch) shows altered microglia metabolism and accelerated aging, impacting oligodendrocyte mitochondrial function. These findings suggest distinct cellular mechanisms in CSch compared to attack-like schizophrenia (ASch).
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Context:
- Schizophrenia is a complex psychiatric disorder with debated underlying neuropathology.
- Microglia and oligodendrocytes play critical roles in white matter integrity and function.
- Distinct clinical subtypes of schizophrenia may exhibit unique cellular alterations.
Purpose:
- To investigate the ultrastructural differences of microglia adjacent to oligodendrocytes in the prefrontal cortex white matter of continuous schizophrenia (CSch) and attack-like schizophrenia (ASch) patients compared to controls.
- To analyze correlations between microglial and oligodendrocyte parameters in both schizophrenia subtypes.
Summary:
- Electron microscopy revealed reduced mitochondrial volume and number in microglia of elderly CSch patients, alongside increased lipofuscin granules, suggesting accelerated aging and metabolic disturbances.
- Microglial nuclear heterochromatin area increased in both CSch and ASch groups, correlating negatively with microglial density in CSch.
- Oligodendrocyte mitochondrial reduction in CSch correlated with microglial mitochondrial changes and lipofuscin accumulation, indicating intercellular metabolic crosstalk.
Impact:
- Findings highlight specific metabolic and nuclear alterations in microglia in CSch, potentially contributing to oligodendrocyte dysfunction.
- The study suggests accelerated microglial aging as a factor in CSch pathophysiology.
- These cellular insights may inform future therapeutic strategies targeting white matter integrity in schizophrenia.
