Psychiatric disturbances regulate the innate immune system in CSF of conscious mice.

Environment may affect brain activity through cerebrospinal fluid (CSF) only if there are regulatory molecules or cascades in CSF that are sensitive to external stimuli. This study was designed to identify regulatory activity present in CSF, better elucidating environmental regulation of brain function. By using cannulation-based sequential CSF sampling coupled with mass spectrometry-based identification and quantification of proteins, we show that the naive mouse CSF harbors, among 22 other pathways, the innate immune system as a main pathway, which was downregulated and upregulated, respectively, by acute stressor (AS) and acute cocaine (AC) administrations. Among novel processes and molecular functions, AS also regulated schizophrenia-associated proteins. Furthermore, AC upregulated exosome-related proteins with a false discovery rate of 1.0 × 10(-)(16). These results suggest that psychiatric disturbances regulate the neuroimmune system and brain disorder-related proteins, presenting a sensitive approach to investigating extracellular mechanisms in conscious and various mouse models of psychiatric disorders.