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Comparative rhythmic transcriptome profiling of human and mouse striatal subregions

Neuropsychopharmacology volume 49, pages 796–805 (2024)Cite this article

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Abstract

The human striatum can be subdivided into the caudate, putamen, and nucleus accumbens (NAc). In mice, this roughly corresponds to the dorsal medial striatum (DMS), dorsal lateral striatum (DLS), and ventral striatum (NAc). Each of these structures have some overlapping and distinct functions related to motor control, cognitive processing, motivation, and reward. Previously, we used a “time-of-death” approach to identify diurnal rhythms in RNA transcripts in these three human striatal subregions. Here, we identify molecular rhythms across similar striatal subregions collected from C57BL/6J mice across 6 times of day and compare results to the human striatum. Pathway analysis indicates a large degree of overlap between species in rhythmic transcripts involved in processes like cellular stress, energy metabolism, and translation. Notably, a striking finding in humans is that small nucleolar RNAs (snoRNAs) and long non-coding RNAs (lncRNAs) are among the most highly rhythmic transcripts in the NAc and this is not conserved in mice, suggesting the rhythmicity of RNA processing in this region could be uniquely human. Furthermore, the peak timing of overlapping rhythmic genes is altered between species, but not consistently in one direction. Taken together, these studies reveal conserved as well as distinct transcriptome rhythms across the human and mouse striatum and are an important step in understanding the normal function of diurnal rhythms in humans and model organisms in these regions and how disruption could lead to pathology.

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Fig. 1: Overlap in rhythmic transcripts between striatal regions in mice.
Fig. 2: Overlapping and distinct rhythmic transcripts and pathways in human and mouse striatum.
Fig. 3: Shift in timing of core clock gene expression between the human and mouse striatum.
Fig. 4: Phase relationships within striatal subregions of mouse and human.
Fig. 5: Peak timing differences between human and mouse striatum.

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Funding

Funding

This work was funded by the National Institutes of Health DA039865, DA046346, MH111601, MH106460, NS127064 (PI: CAM), and MH128763 (PI: KDK), the Brain and Behavior Research Foundation (30823 (P&S Fund), PI: KDK), and the Wood Next Foundation (PI: CAM) (https://www.woodnext.org/).

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Authors and Affiliations

  1. Department of Psychiatry, Translational Neuroscience Program, Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA

    Kaitlyn A. Petersen, Lauren M. Depoy, Madeline R. Scott, Vaishnavi G. Shankar, Jennifer N. Burns, Allison J. Cerwensky, Sam-Moon Kim, Kyle D. Ketchesin & Colleen A. McClung

  2. Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA

    Wei Zong & George C. Tseng

Authors
  1. Kaitlyn A. Petersen
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Contributions

Conceptualization: KAP, CAM; Methodology: GT, CAM; Data acquisition: KAP, LMD, MRS, VGS, JNB, AJC, SMK, KDK; Data analysis: KAP, WZ; Writing: KAP, LMD, MRS, KDK, CAM.

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Correspondence to Colleen A. McClung.

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Petersen, K.A., Zong, W., Depoy, L.M. et al. Comparative rhythmic transcriptome profiling of human and mouse striatal subregions. Neuropsychopharmacol. 49, 796–805 (2024). https://doi.org/10.1038/s41386-023-01788-w

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