Transcriptome sequencing of the choroid plexus in schizophrenia

Abstract

The choroid plexus (CP) has a key role in maintaining brain homeostasis by producing cerebrospinal fluid (CSF), by mediating transport of nutrients and removing metabolic products from the central nervous system and by responding to peripheral inflammatory signals. Although abnormal markers of immune response and inflammation are apparent in individuals with schizophrenia, the CP of these individuals has not been characterized. We therefore sequenced mRNA from the CP from two independent collections of individuals with schizophrenia and unaffected controls. Genes related to immune function and inflammation were upregulated in both collections. In addition, a co-expression module related to immune/inflammation response that was generated by combining mRNA-Seq data from both collections was significantly associated with disease status. The immune/inflammation-related co-expression module was positively correlated with levels of C-reactive protein (CRP), cortisol and several immune modulator proteins in the serum of the same individuals and was also positively correlated with CRP, cortisol and pro-inflammatory cytokines in the frontal cortex of the same individuals. In addition, we found a substantial number of nodes (genes) that were common to our schizophrenia-associated immune/inflammation module from the pooled data and a module we generated from lippopolysaccharides-treated mouse model data. These results suggest that the CP of individuals with schizophrenia are responding to signals from the periphery by upregulating immune/inflammation-related genes to protect the brain and maintain the homeostasis but nevertheless fails to completely prevent immune/inflammation related changes in the brain.