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Day-night fluctuations in choroid plexus transcriptomics and cerebrospinal fluid metabolomics
Beatriche Louise Edelbo1, Søren Norge Andreassen1, Annette Buur Steffensen1
1Department of Neuroscience, University of Copenhagen, 2200 Copenhagen, Denmark.
PNAS Nexus
|August 24, 2023
Summary
Cerebrospinal fluid (CSF) secretion shows daily rhythm, influenced by circadian factors, not sleep. This study identifies key genes and metabolites in the rat choroid plexus and CSF, revealing molecular drivers of this diurnal CSF regulation.
Area of Science:
- Neuroscience
- Physiology
- Chronobiology
Background:
- Cerebrospinal fluid (CSF) protects the brain and aids waste removal.
- CSF secretion rate increases during the dark phase, suggesting circadian regulation.
- Understanding CSF dynamics is crucial for brain health and waste clearance.
Purpose of the Study:
- To identify molecular drivers of diurnal CSF secretion rate modulation.
- To investigate changes in rat choroid plexus transcriptome and CSF metabolome.
- To explore potential pathways for modulating CSF dynamics in disease.
Main Methods:
- RNA sequencing (RNA-seq) of rat choroid plexus.
- Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) for CSF metabolomics.
- Joint pathway analysis of transcriptomic and metabolomic data.
Main Results:
- Significant diurnal fluctuations observed in 19 CSF metabolites.
- Differential expression of 2,778 choroid plexus genes between light and dark phases.
- Circadian rhythm-related genes and transport mechanisms identified in choroid plexus.
Conclusions:
- Substantial light-dark phase-mediated transcriptional and metabolic changes occur in the rat choroid plexus and CSF.
- Identified molecular pathways provide targets for future research into CSF regulation.
- Findings may lead to therapeutic strategies for modulating CSF dynamics in neurological disorders.
