Ultrastructural disturbances in microglia-neuron interactions in the head of the caudate nucleus in schizophrenia

Previously we found altered microglia-neuron interactions in the prefrontal cortex in schizophrenia. We hypothesized that microglia-neuron interactions may be dysregulated in the caudate nucleus in schizophrenia. A postmortem ultrastructural morphometric study was performed to investigate satellite microglia (SatMg) and adjacent neurons in the head of the caudate nucleus in 21 cases of schizophrenia and 20 healthy controls. We found increased microglial density in young schizophrenia patients compared to elderly controls. Volume density (Vv) and the number (N) of mitochondria were lower and total area of vacuoles of endoplasmic reticulum was higher in SatMg in the schizophrenia group compared to controls. The mitochondrial decline has progressed with age and illness duration. Areas of neuronal somata, nucleus, mitochondria and vacuoles of endoplasmic reticulum were significantly higher in schizophrenia compared to controls. These neuronal parameters were positively correlated with area and Vv of vacuoles of endoplasmic reticulum in SatMg in the schizophrenia group but not in the control group. Besides, area of mitochondria in neurons was negatively correlated with N of mitochondria in SatMg. Vv of lipofuscin granules in neurons was higher in elderly patients compared to young patients and was positively correlated with age, illness duration and Vv of lipofuscin granules in SatMg in the schizophrenia group. The disturbances of SatMg-neuronal interactions may be related to the endoplasmic reticulum stress, alterations and deficit of mitochondria in SatMg due to chronic stress, activation and priming of SatMg followed by neurotoxicity. SatMg may participate in neuronal aging in schizophrenia.