Increasing evidence coming from neuroimaging and post-mortem studies support the notion that GABAergic neurons, and oligodendrocytes play a key role in the pathogenesis of schizophrenia and mood disorders. Moreover, neuroinflammation might contribute to the pathology of neurons and oligodendroglia in these disorders. N. Uranova will present the results of post-mortem ultrastructural morphometric studies. Volume fraction and number of mitochondria were significantly decreased, while volume fraction of vacuoles of endoplasmic reticulum and lipofuscin granules were significantly increased in oligodendrocytes adjacent to either microglia or myelin in schizophrenia and in patients displaying predominantly positive symptoms. Lymphocyte infiltration in the brain in psychiatric disorders is indicative of an impairment or altered state of the blood-brain barrier and supports the role of the immune system in a relevant subgroup of patients. K. Schlaaff assessed regional densities of T and B lymphocytes and subsets in post-mortem brains of patients with schizophrenia and major depression. Using automated high-resolution image acquisition and a data-driven approach on data, he identified a subgroup of patient with lymphocyte infiltration. Conventional drugs may increase GABA interneuron transmission and thus can be used to treat some of the neuropsychiatric disorders. A. Gos will summarize previous post-mortem studies on this topic. Moreover, she will provide a first glance on ongoing histological studies on the role of GABAergic interneurons in the modulation of the reward system of opioid-addicted patients. F. Raabe will talk about the promise and limitations of human induced pluripotent stem cells (hiPSCs) with the generation of neuronal and glial cells to dissect cell-type specific contributions in schizophrenia. iPSC-based technology might reveal so far hidden molecular principles of the pathogenesis and could pave the way towards new treatment options.
Ultrastructural pathology of oligodendrocytes adjacent to microglia in prefrontal white matter in schizophrenia
Natalya Uranova, Moskau (Russian Federation)
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Natalya Uranova, Moskau (Russian Federation)
Objective. Microglial activation has been proposed to be involved in the pathophysiology of schizophrenia. We hypothesized that dystrophic alterations of oligodendrocytes previously reported in the prefrontal white matter in schizophrenia might be associated with microglial activation in the acute state of the disease.
Material and Methods. White matter of the prefrontal cortex (BA10) was studied in postmortem brain tissue from 21 schizophrenia cases and 20 normal controls. The schizophrenia group included 12 subjects with predominantly positive symptoms (SPPS) and 9 subjects with predominantly negative symptoms (SPNS). 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.
Results/Discussion. Cell density of oligodendrocytes was not changed in the schizophrenia group as compared to controls. Vv of mitochondria was significantly decreased, Vv of vacuoles and N of lipofuscin were increased in oligodendrocytes adjacent to either microglia or myelin in the SPPS subgroup as compared to the control group. Only in oligodendrocytes adjacent to microglia N of mitochondria was decreased, Vv of lipofuscin was increased in the SPPS subgroup as compared to controls and Vv of vacuoles was higher in the SPPS subgroup as compared to the SPNS subgroup. There was no effect of clinical subgroups on the parameters of peri-capillary and peri-neuronal oligodendrocytes. The data suggest that dystrophic damage of oligodendrocytes adjacent to microglia might be associated with microglia activation in the schizophrenia cases with predominantly positive symptoms.
The role of GABAergic interneurons in mood disorders and modulation of the reward system by opioids
Anna Gos, Gdańsk (Poland)
Induced pluripotent stem cells and oligodendrocytes in schizophrenia research
Florian Raabe, München (Germany)
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Florian Raabe, München (Germany)
The advent of individual patient-derived human-induced pluripotent stem cells (hiPSCs) holds great potential for understanding the molecular basis of the aetiopathogenesis of genetically complex psychiatric diseases such as schizophrenia. With the differentiation of principally any neuronal and glial cell type, hiPSC-based technology opens a new era in biological psychiatry. High costs, limited scalability, cellular variability, cellular robustness and patient heterogeneity are important limitations and represent crucial challenges. However, the hiPSC field is rapidly evolving and offers more and more possibilities and solutions. hiPSC-based technology might reveal so far hidden molecular principles of the pathogenesis and could pave the way towards new treatment options and precision medicine.