Impaired monocyte activation in schizophrenia: ultrastructural abnormalities and increased IL-1β production
Natalya A Uranova1, P D Bonartsev2, L V Androsova3
1Laboratory of Clinical Neuropathology, Mental Health Research Centre, Zagorodnoe Shosse 2, Moscow, 117152, Russia. uranovan@mail.ru.
Abstract:
Monocyte activation is consistently reported in patients with schizophrenia (SZ). We aimed to study the ultrastructure of monocytes and monocyte production of IL-1β in drug-free patients with SZ and controls. Monocytes from young (18-30 y.o.) healthy and SZ men in relapse were studied. Electron microscopy and morphometry were applied to estimate areas of monocytes, volume density (Vv), areas, and number of organelles. The production IL-1β by monocytes was estimated by the ELISA method. Group differences were examined using ANCOVA. Pearson's correlation coefficients were used to examine the effects of possible confounding variables. Correlation analyses were applied to detect the relationships between the parameters of monocytes measured and between the parameters measured and the IL-1β production. Area of nucleolus, Vv and area of mitochondria and lysosomes, and the number of lysosomes were significantly increased in patients as compared to controls. Area of mitochondria was correlated significantly with Vv and area of lysosomes, and the number of lysosomes was significantly correlated with area of monocyte and Vv of vacuoles only in the control group. The production of IL-1β by monocytes was higher in patients than in controls (p = 0.01) and was correlated with Vv of lysosomes (r = 0.68, p = 0.04) and area of lysosomes (r = 0.78, p = 0.013). The data provide new evidence for over activation of monocytes in SZ and disturbed metabolic relationships between lysosomes, mitochondria, and vacuoles.
Insights
Monocytes in individuals with schizophrenia show increased size and organelle content, alongside higher Interleukin-1 beta (IL-1β) production. These findings suggest heightened monocyte activation and altered cellular metabolism in schizophrenia patients.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Psychiatry
Background:
- Monocyte activation is a known factor in schizophrenia (SZ).
- Previous research indicates potential cellular alterations in SZ patients.
Purpose of the Study:
- To investigate the ultrastructure of monocytes in drug-free schizophrenia patients.
- To examine Interleukin-1 beta (IL-1β) production by monocytes in relation to cellular morphology.
Main Methods:
- Electron microscopy and morphometry were used to analyze monocyte ultrastructure.
- Enzyme-linked immunosorbent assay (ELISA) measured IL-1β production.
- Statistical analyses included ANCOVA and Pearson correlation.
Main Results:
- Schizophrenia patients exhibited significantly larger nucleoli, mitochondria, and lysosomes compared to controls.
- Monocytes from schizophrenia patients produced higher levels of IL-1β.
- IL-1β production correlated with lysosomal parameters in patients.
Conclusions:
- Schizophrenia is associated with monocyte hyperactivity and altered intracellular organelle dynamics.
- Disturbed metabolic interactions between lysosomes, mitochondria, and vacuoles may contribute to pathophysiology in schizophrenia.
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