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. Author manuscript; available in PMC: 2023 Jul 1.
Published in final edited form as: Biol Psychiatry. 2022 Feb 18;92(1):68–80. doi: 10.1016/j.biopsych.2022.02.007

Figure 2. Nucleus accumbens astrocytes are highly rhythmic at the transcriptome level.

Figure 2.

Among the 12,739 genes identified in NAc astrocytes, approximately 43.3% of genes exhibited rhythmic expression across the 6 ZTs sampled (ZT2,6,10,14,18,22; n=4–5 per ZT, JTK_Cycle), or 5,527 genes at the Bonferroni-adjusted p-value cutoff of p<0.05. Even using the most stringent statistical cutoff (Benjamini-Hochberg q-value cutoff of q<0.0001), approximately ~9% of transcripts still display diurnal rhythmicity, or 1,141 genes. (B) Phase analysis through radar plotting of top rhythmic transcripts (p<0.05) and heatmap visualization of the top 200 rhythmic genes reveal a majority of rhythmic transcripts peak between ZT14 and ZT18, coinciding with the dark phase / active phase. The radar plot perimeter axis represents ZT, while the inner axis is the number of genes with peak expression at a given ZT. Heatmap displays Z-transformed expression for each of the top 200 statistically rhythmic genes (as determined by JTK_Cycle), ranked in descending order along the Y-axis (rows) and each subject ordered by ZT along the x-axis (columns). The white bar indicates lights on (ZT2,6,10) and the black bars indicate lights off (ZT14,18,22). (C) IPA pathway analysis and Metascape Gene Ontology (GO) Biological Process analysis revealed both circadian and metabolic-related processes enriched among the top rhythmic genes. Notable pathways/processes include circadian rhythm signaling and circadian regulation of gene expression, as well as NRF2-mediated oxidative stress response, regulation of ATPase activity, and glucocorticoid receptor signaling. Red line in bar graphs indicates significance threshold of p<0.05 or −log10(p-value) > 1.3. (D) Core circadian genes are among the top rhythmic genes and show expression patterns that align with previously established functional relationships; i.e., Arntl (gene that encodes BMAL1) is anti-phasic with Per2 and Nr1d1). (E) Among the top enriched rhythmic GO biological processes, the circadian regulation of gene expression and glucocorticoid receptor signaling node clusters show a high degree of interconnectivity.