In the brain, inflammation is initiated by a myriad of processes. For example, accumulation of DNA damage and associated factors can lead to the release of proinflammatory cytokines via microglia activation12,13. Prolonged proinflammatory states in the brain result in elevated oxidative stress and altered metabolism in glia12–15 and neurons13,16,17. Neuroinflammation and DNA damage are also central to neurodegenerative processes2,5,9, which have been related to OUD18–23. With the advent of high-throughput single cell technologies, such as single nuclei RNA-sequencing (snRNA-seq), deeper investigations into the roles of inflammation and DNA damage in OUD can be achieved in human brain. Beyond resolving cell type-specific molecular alterations previously found with other approaches (e.g., bulk tissue RNA-seq)5, snRNA-seq in human brain also offers the possibility of unmasking new biological relationships between neural cell types and disease.
