Defining diurnal fluctuations in mouse choroid plexus and CSF at high molecular, spatial, and temporal resolution
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 TtrmNeonGreen 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 22, 2023
- Source ID
- 10.1038/s41467-023-39326-3
Entities
People
- Aja Pragana
- Amanda Vernon
- Boryana Petrova
- Bradford Grant
- Fan Gao
- Fortunate F. Chifamba
- Frederick B. Shipley
- Hannah Hawks-mayer
- Huixin Xu
- Jonathan O. Lipton
- Joshua P. Head
- Maria Lehtinen
- Mark L Andermann
- Michael J Holtzman
- Morgan L. Shannon
- Myriam Heiman
- Naama Kanarek
- Neil Dani
- Paul A. Soden
- Peter N. Kalugin
- Ryann M Fame
- Suhasini Gupta
- Yong Zhang
Organizations
- National Institutes of Health
- New York Stem Cell Foundation
- United States Department of Health and Human Services