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-naïve 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.

Additional Metadata
Keywords Drug target, Inflammation, Microglia, MTORC1, Phosphoflow, Psychiatric disorders, Stat3
Persistent URL dx.doi.org/10.1016/j.bbi.2017.10.003, hdl.handle.net/1765/102269
Journal Brain, Behavior, and Immunity
Grant This work was funded by the European Commission 7th Framework Programme; grant id fp7/286334 - Advanced Immuno-neuro-endocrine Diagnostics in Psychiatry (PSYCH-AID)
Citation
van Rees, G.F. (Geertje Frederique), Lago, S.G, Cox, D, Tomasik, J.J, Rustogi, N. (Nitin), Weigelt, K, … Bahn, S. (2017). Evidence of microglial activation following exposure to serum from first-onset drug-naïve schizophrenia patients. Brain, Behavior, and Immunity. doi:10.1016/j.bbi.2017.10.003