Comparative transcriptomic rhythms in the mouse and human prefrontal cortex.

Area of Science:

• Neuroscience
• Genomics
• Chronobiology

Background:

• Prefrontal cortex (PFC) alterations are linked to psychiatric disorders.
• Circadian gene expression rhythms exist in the brain, including the PFC, and are disrupted in disease.
• Translational research is challenged by human PFC specialization compared to rodents.

Purpose of the Study:

• To compare transcriptomic rhythms between mouse medial PFC (mPFC) and human anterior cingulate cortex (ACC) and dorsolateral PFC (DLPFC).
• To provide a foundation for translational studies on molecular rhythms.
• To investigate sex-specific differences in cross-species transcriptomic rhythms.

Main Methods:

• RNA sequencing was employed for transcriptomic analysis.
• A sex-specific, cross-species comparison was conducted.
• Rhythmic transcripts were analyzed in mouse mPFC and human ACC/DLPFC.

Main Results:

• Circadian rhythm signaling is conserved across species and PFC subregions.
• A sex-dependent phase shift in core clock gene expression exists between mouse mPFC and human PFC.
• Transcriptomic rhythm identity is largely unique, with highest overlap between mouse mPFC and human ACC in females.
• Core biological processes show enrichment for rhythmic transcripts, with regional and sex-specific variations.

Conclusions:

• Transcriptomic rhythms are evolutionarily conserved but show significant advancement in the human PFC.
• Cross-species differences, particularly sex-specific ones, must be considered in animal models for psychiatric disease research.
• This study provides crucial insights for developing more accurate translational models.