Abstract
Schizophrenia (SCZ) is a complex psychiatric disorder that is one of the leading causes of disability worldwide and carries a disproportionately high financial burdens on healthcare systems and individual patients due to the chronic nature of the symptoms. One major roadblock in advancing SCZ treatment options is the need for a better understanding of pathways involved in SCZ pathophysiology that could offer new therapeutic targets for treating the disorder. A popular theory that has emerged is the Microglia Hypothesis of Schizophrenia which proposes that microglia, the resident immune cells of the brain, take on reactive phenotypes and release inflammatory cytokines that may drive neuroinflammation and contribute to SCZ pathophysiology. Within the context of the Microglial Hypothesis, is growing interest in identifying the specific molecular mechanisms that could drive microglial-mediated neuroinflammation in SCZ. The inflammasome pathway has become a popular candidate mechanism based on the presence of inflammasome derived cytokines in patients with SCZ, reports showing increased inflammasome activity in animal models of SCZ, and findings showing that some antipsychotics may function through targeting the inflammasome. To date, there have been very few reports exploring inflammasome protein expression in patients with SCZ, highlighting the need for a better understanding of inflammasome changes in human tissue from patients diagnosed with SCZ.
This study aims to characterize microglial alterations in brains from human donors with SCZ and explore protein expression changes that could indicate inflammasome activation in brains from donors with SCZ. Here I show that in brains from donors with SCZ there are not only increases in microglial density and shifts in morphology towards pro-inflammatory phenotypes, but there is also increased expression of multiple inflammasome proteins in microglial cell bodies. The results here suggest that inflammasome activation in microglia may drive neuroinflammation in SCZ and could offer a novel therapeutic target.