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Evidence of microglial activation following exposure to serum from first-onset drug-naive schizophrenia patients

van Rees, Geertje Frederique
Lago, Santiago Guillermo
Cox, David Alan
Tomasik, Jakub
Rustogi, Nitin
Weigelt, Karin
Özcan Kabasakal, Süreyya
Cooper, Jason
Drexhage, Hemmo
Leweke, F. Markus
Bahn, Sabine
Abnormal activation of brain microglial cells is widely implicated in the pathogenesis of schizophrenia. Previously the pathophysiology of microglial activation was considered to be intrinsic to the central nervous system. We hypothesised that due to their perivascular localization, microglia can also be activated by factors present in circulating blood. Through application of high-content functional screening, we show that peripheral blood serum from first-onset drug-naive schizophrenia patients is sufficient to provoke microglial cell signalling network responses in vitro which are indicative of proinflammatory activation. We further explore the composition of the serum for the presence of analytes, with the potential to activate microglia, and the utility of the resultant microglial cellular phenotype for novel drug discovery.