Modeling Microglia in Schizophrenia: Illumination of the Immune Perspective

Abstract

The immune system is the defense system of the body and protects against body entering pathogens. The brain features its own immune cell, named microglia. These microglia have been implicated in various psychiatric diseases, including schizophrenia. In this thesis we describe the development of several microglia cell models, which we used in the laboratory to study a schizophrenia profile of this cell. We used two distinct methods. First, we used monocytes that we enriched from the blood samples of patients with schizophrenia and controls. We exposed these cells to a mixture of factors that induced the differentiation of a microglia-like cell (MoGli). With this cell model we identified a schizophrenia-profile in immune cells from patients. Second, we used induced pluripotent stem cells. We cultured and differentiated these cells into 3D replica's of the human brain with a 4mm diameter. The protocol developed in this thesis describes an important adaptation of the original protocol as it led to the generation of microglia aside of nerve cells in these mini-brains. This important addition enabled us to study the role of an important risk factor of schizophrenia: prenatal infection. By exposing mini-brains to bacterial proteins we investigated the effect of infection on brain development. The human brain seemed surprisingly resistant to an infection, in contrast to earlier results obtained in mice experiments. The research performed in this thesis led to new insights into the disease pathogeneis of schizophrenia and initiated new research possibilities.