Glia in health and disease

Schizophrenia is a severe chronic psychiatric disorder characterized by positive symptoms (e.g. hallucinations, delusions, disorganized speech), negative symptoms (e.g. loss of emotional expressions, lack of interest) and cognitive decline. Schizophrenia is often diagnosed at late adolescence or early adulthood, but in retrospect the first signs of the disease are most often present years before. Despite decades of intensive research the pathogenesis of schizophrenia is still largely unclear. We know that both genetic and environmental factors contribute to the disease. In addition, most research indicate that neurodevelopmental processes and synaptic functioning are affected. From epidemiological and genetic studies it is becoming more and more clear that the immune system contributes to schizophrenia pathogenesis. However, which immune system pathway(s) and which immune cell type is affected is yet unknown. It is clear that immune system pathways in the central nervous system are not only involved in neuroinflammation but also in neurodevelopmental processes, including neurogenesis and synaptic pruning. In our research we therefore investigate the role of immune processes in schizophrenia, hypothesizing that the immune system in schizophrenia is affected by genetic or environmental factors leading to dysfunction of these pathways in neurodevelopment and synaptic functioning. We focus on the role of microglia and to a lesser extent astrocytes. We use postmortem brain material of patients and controls to study these cells in situ, but also ex vivo by isolating the cells from fresh brain tissue. We investigate the phenotype and function of these cells with special attention for the neuron-glia interacting molecules. In addition, we use in vitro models to study the cells by culturing monocytes from patients and controls to a microglia-like phenotype. With this project we aim to find target for novel treatment regimens, potentially with currently available immunemodulatory drugs.