TY - JOUR
T1 - Defining diurnal fluctuations in mouse choroid plexus and CSF at high molecular, spatial, and temporal resolution
AU - Fame, Ryann M.
AU - Kalugin, Peter N.
AU - Petrova, Boryana
AU - Xu, Huixin
AU - Soden, Paul A.
AU - Shipley, Frederick B.
AU - Dani, Neil
AU - Grant, Bradford
AU - Pragana, Aja
AU - Head, Joshua P.
AU - Gupta, Suhasini
AU - Shannon, Morgan L.
AU - Chifamba, Fortunate F.
AU - Hawks-Mayer, Hannah
AU - Vernon, Amanda
AU - Gao, Fan
AU - Zhang, Yong
AU - Holtzman, Michael J.
AU - Heiman, Myriam
AU - Andermann, Mark L.
AU - Kanarek, Naama
AU - Lipton, Jonathan O.
AU - Lehtinen, Maria K.
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85162757887&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-39326-3
DO - 10.1038/s41467-023-39326-3
M3 - Article
C2 - 37349305
AN - SCOPUS:85162757887
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 3720
ER -