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Comparative rhythmic transcriptome profiling of human and mouse striatal subregions.

Kaitlyn A Petersen1, Wei Zong2, Lauren M Depoy1

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

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PubMed
Summary

This study reveals conserved and distinct daily molecular rhythms in the human and mouse striatum. Notably, RNA processing rhythms in the human nucleus accumbens are not conserved in mice, suggesting unique human adaptations.

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Area of Science:

  • Neuroscience
  • Chronobiology
  • Molecular Biology

Background:

  • The human striatum, comprising the caudate, putamen, and nucleus accumbens (NAc), plays roles in motor control, cognition, and reward.
  • Previous research identified diurnal RNA transcript rhythms in human striatal subregions using a
  • This study aimed to identify and compare molecular rhythms in mouse striatal subregions to human data, investigating conserved and species-specific patterns.

Purpose of the Study:

  • To identify molecular rhythms in mouse striatal subregions (dorsal medial striatum, dorsal lateral striatum, ventral striatum).
  • To compare these rhythms with previously identified diurnal rhythms in human striatal subregions.
  • To investigate species-specific differences in transcriptome rhythms, particularly in RNA processing.

Main Methods:

  • Collected striatal subregions from C57BL/6J mice at 6 different times of day.
  • Analyzed RNA transcripts to identify molecular rhythms.
  • Compared rhythmic transcripts and pathways between mouse and human striatal data.

Main Results:

  • Identified significant overlap in rhythmic transcripts related to cellular stress, energy metabolism, and translation between human and mouse striata.
  • Discovered that small nucleolar RNAs (snoRNAs) and long non-coding RNAs (lncRNAs) exhibit high rhythmicity in the human NAc, a pattern not observed in mice.
  • Observed alterations in the peak timing of overlapping rhythmic genes between species, without a consistent directional shift.

Conclusions:

  • The human and mouse striata share conserved diurnal transcriptome rhythms, particularly in metabolic and stress-response pathways.
  • Rhythmicity in RNA processing, specifically involving snoRNAs and lncRNAs in the nucleus accumbens, appears to be a uniquely human characteristic.
  • Understanding these conserved and distinct diurnal rhythms is crucial for comprehending normal striatal function and the potential impact of their disruption on neurological disorders.