Defining diurnal fluctuations in mouse choroid plexus and CSF at high molecular, spatial, and temporal resolution

Ryann M. Fame, Peter N. Kalugin, Boryana Petrova, Huixin Xu, Paul A. Soden, Frederick B. Shipley, Neil Dani, Bradford Grant, Aja Pragana, Joshua P. Head, Suhasini Gupta, Morgan L. Shannon, Fortunate F. Chifamba, Hannah Hawks-Mayer, Amanda Vernon, Fan Gao, Yong Zhang, Michael J. Holtzman, Myriam Heiman, Mark L. AndermannNaama Kanarek, Jonathan O. Lipton, Maria K. Lehtinen

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Transmission and secretion of signals via the choroid plexus (ChP) brain barrier can modulate brain states via regulation of cerebrospinal fluid (CSF) composition. Here, we developed a platform to analyze diurnal variations in male mouse ChP and CSF. Ribosome profiling of ChP epithelial cells revealed diurnal translatome differences in metabolic machinery, secreted proteins, and barrier components. Using ChP and CSF metabolomics and blood-CSF barrier analyses, we observed diurnal changes in metabolites and cellular junctions. We then focused on transthyretin (TTR), a diurnally regulated thyroid hormone chaperone secreted by the ChP. Diurnal variation in ChP TTR depended on Bmal1 clock gene expression. We achieved real-time tracking of CSF-TTR in awake Ttr mNeonGreen mice via multi-day intracerebroventricular fiber photometry. Diurnal changes in ChP and CSF TTR levels correlated with CSF thyroid hormone levels. These datasets highlight an integrated platform for investigating diurnal control of brain states by the ChP and CSF.

Original languageEnglish
Article number3720
JournalNature communications
Volume14
Issue number1
DOIs
StatePublished - Dec 2023

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