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Sex Differences in Molecular Rhythms in the Human Cortex.

Ryan W Logan1, Xiangning Xue2, Kyle D Ketchesin3

  • 1Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts; Center for Systems Neurogenetics of Addiction, The Jackson Laboratory, Bar Harbor, Maine.

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Summary
This summary is machine-generated.

Male and female brains show distinct daily gene expression patterns. These sex differences in the dorsolateral prefrontal cortex and anterior cingulate cortex may explain variations in physiological and behavioral rhythms.

Keywords:
Molecular rhythmPostmortem brainSex difference

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Area of Science:

  • Neuroscience
  • Genomics
  • Chronobiology

Background:

  • Diurnal gene expression rhythms are known in the human brain.
  • Previous research indicated sex differences in circadian gene expression timing.
  • The extent of sex differences in large-scale cortical transcriptional rhythms remained unknown.

Purpose of the Study:

  • To investigate sex differences in diurnal gene expression rhythms across the human cortex.
  • To compare transcriptional rhythmicity in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) between males and females.
  • To explore potential links between molecular rhythms and sex-specific physiological/behavioral patterns.

Main Methods:

  • RNA sequencing of human postmortem DLPFC and ACC samples from males and females.
  • Analysis of diurnal rhythmicity, sex differences, and phase concordance in gene expression.
  • Pathway and transcription factor analyses of rhythmic genes.

Main Results:

  • While canonical circadian genes showed similar rhythms in both sexes, the broader transcriptome revealed significant sex differences.
  • Males exhibited more rhythmic transcripts in the DLPFC; females showed more in the ACC.
  • Female ACC showed diurnal rhythms in synaptic transmission, including GABAergic and cholinergic neurotransmission.

Conclusions:

  • Significant sex differences exist in the molecular rhythms of genes within the human DLPFC and ACC.
  • These findings offer mechanistic insights into circadian-dependent and sex-specific modulation of neurotransmission and synaptic function.