Together, these data suggest the importance of glial-associated synaptic gene expression in schizophrenia, while emphasizing the heterogeneity of pathways that might be mechanistically complicit in its dysregulation. These data also highlight the point that while the neuronal localization of these synaptic proteins has long been recognized, their synthesis by glia and synaptic contributions thereof have not been specifically discussed, although cell type-specific transcriptional databases have noted significant glial expression of these genes (Zhang et al., 2014). Since NRXN1, a synapse-associated transcript closely linked to schizophrenia (Sudhof, 2008), was one of the most strongly and consistently down-regulated glial genes across our patients, we verified the down-regulation of its expression by SCZ glia, by immunoblotting CD140a-sorted, neuron-free isolates of SCZ and control hGPCs. Western blots revealed that neurexin-1 was indeed abundantly expressed by human GPCs, and that neurexin-1 protein levels were sharply lower in otherwise matched SCZ hGPCs (Figure S5).
