Fig. 4: Elevated markers of DNA damage in striatal neurons associated with OUD and chronic morphine in rhesus macaque.
From: Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder
a Schematic of the application of DNA damage gene signatures from a mouse model of Alzheimer’s Disease13 to score DNA damage in human and rhesus macaque striatal neurons. b Boxplot of individual-level pseudobulk average DNA damage scores across striatal neurons between unaffected individuals and individuals with opioid use disorder (OUD) (PDx = 0.046, two-sided linear regression, 15 degrees of freedom). Each data point comes from N = 22 biologically independent samples of caudate and putamen from M = 12 individuals. c Violin-boxplot of cell type-level pseudobulk average DNA damage scores between unaffected individuals and individuals with OUD. The significant cell type interaction effect with diagnosis two-sided P-values from one linear regression are reported above each plot (two-sided linear regression, 114 degrees of freedom). Each data point comes from each neuronal cell type from N = 12 biologically independent individuals. d Schematic of chronic morphine exposure or unexposed rhesus macaques (N = 4 individuals per treatment). e Boxplots of individual level pseudobulk average DNA damage scores across striatal neurons or neuronal subtypes between control individuals or those exposed to chronic morphine. The effect of morphine in all striatal neurons is one linear regression (two-sided linear regression, 2 degrees of freedom). The morphine by cell type interaction effect for each striatal neuron subtype is another linear regression (two-sided linear regression, 20 degrees of freedom). The significant effect of chronic morphine treatment P-values from linear regressions are reported above each plot. (*P < 0.05; **P < 0.01; ***P < 0.001). Each data point comes from all neuronal cell types or each neuronal cell type from N = 8 biologically independent rhesus macaque striatal samples. Schematics in (a, d) created using BioRender.com. Source data are provided as a Source Data file. Boxplots in 4b-c and 4e are plotted as median, the 25% and 75% percentiles, and non-outlier maxima and minima.
