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[Microglial reactivity in the prefrontal cortex in different types of schizophrenia]
1Mental Health Research Centre, Moscow, Russia.
Objective:
To estimate microglial density and the ultrastructural parameters of microglia in the prefrontal cortex in chronic attack-like and continuous schizophrenia as compared to healthy controls.
Material And Methods:
Postmortem electron microscopic morphometric study of microglia was performed in the prefrontal cortex (layer 5, Brodmann' area 10). Ten cases of attack-like schizophrenia, 9 cases of continuous schizophrenia and 20 controls were studied. Microglial density, areas of cell and nucleus, nucleus/cytoplasm ratio, volume fraction and the number of mitochondria, vacuoles of endoplasmic reticulum and lipofuscin granules were estimated. ANCOVA was used for statistical analysis.
Results:
A significant decrease in volume fraction and the number of mitochondria and increase in these parameters of lipofuscin granules were found in both groups as compared to the control group. The group of attack-like schizophrenia showed a significant increase in area of vacuoles as compared to the control group, a significant increase in microglial density as compared to controls and in the young (≤50 yrs.old) subgroup as compared to the elderly (>50 yrs.old) control subgroup. In this group, areas of cell and nucleus were significantly higher in the young subgroup as compared to elderly controls, the elderly subgroup of attack-like schizophrenia and the young subgroup of continuous schizophrenia. An increase in the areas of microglia and the nucleus of microglia in young patients was found in comparison with the elderly from the control group, elderly patients with attack-like schizophrenia and young patients with continuous schizophrenia. Significant negative correlations of areas of cell and nucleus and the number of mitochondria with age and positive correlations of area of lipofuscin granules with age and illness duration were found in attack-like schizophrenia in contrast to continuous schizophrenia.
Conclusion:
Chronic attack-like schizophrenia is associated with increased reactivity in young age and dystrophic changes of microglia progressive with age and illness duration. Continuous schizophrenia is associated with reduced microglial reactivity, dystrophic and non-progressive changes of microglia.
Insights
Microglial changes in schizophrenia differ by disease course. Attack-like schizophrenia shows increased reactivity and age-progressive dystrophic changes, while continuous schizophrenia exhibits reduced, non-progressive microglial alterations.
Area of Science:
- Neuroscience
- Psychiatry
- Cell Biology
Background:
- Schizophrenia is a chronic mental disorder with complex neuropathology.
- Microglia, the brain's immune cells, play a crucial role in neuroinflammation and synaptic plasticity.
- Alterations in microglial morphology and density have been implicated in schizophrenia pathogenesis.
Purpose of the Study:
- To quantitatively assess microglial density and ultrastructural characteristics in the prefrontal cortex of patients with chronic attack-like and continuous schizophrenia compared to healthy controls.
- To investigate age- and illness duration-related changes in microglial morphology in different schizophrenia subtypes.
Main Methods:
- Postmortem electron microscopic morphometric analysis of microglia in the prefrontal cortex (Brodmann' area 10, layer 5).
- Study included 10 cases of attack-like schizophrenia, 9 cases of continuous schizophrenia, and 20 controls.
- Parameters analyzed included microglial density, cell/nucleus area, nucleus/cytoplasm ratio, mitochondrial number, and vacuole/lipofuscin granule content.
Main Results:
- Both schizophrenia groups showed decreased mitochondrial volume fraction and increased lipofuscin granules compared to controls.
- Attack-like schizophrenia exhibited increased microglial density and vacuole area, particularly in younger individuals.
- Age and illness duration correlated with microglial changes in attack-like schizophrenia, but not in continuous schizophrenia.
Conclusions:
- Attack-like schizophrenia is associated with heightened microglial reactivity in youth and age- and illness duration-dependent dystrophic changes.
- Continuous schizophrenia is characterized by reduced microglial reactivity and non-progressive dystrophic alterations.
- These findings highlight distinct microglialpathways in different schizophrenia subtypes, suggesting potential therapeutic targets.
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