Publication Date
5-1-2024
Journal
Nature Neuroscience
DOI
10.1038/s41593-024-01604-8
PMID
38528202
PMCID
PMC11088999
PubMedCentral® Posted Date
5-25-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Animals, Mice, Cerebrospinal Fluid, Hydrocephalus, Ion Channels, Lymphatic Vessels, Mechanotransduction, Cellular, Meninges, Mice, Inbred C57BL, Mice, Transgenic, Pyrazines, Thiadiazoles, Humans, Developmental disorders, Hydrocephalus, Cardiovascular biology, Brain
Abstract
Piezo1 regulates multiple aspects of the vascular system by converting mechanical signals generated by fluid flow into biological processes. Here, we find that Piezo1 is necessary for the proper development and function of meningeal lymphatic vessels and that activating Piezo1 through transgenic overexpression or treatment with the chemical agonist Yoda1 is sufficient to increase cerebrospinal fluid (CSF) outflow by improving lymphatic absorption and transport. The abnormal accumulation of CSF, which often leads to hydrocephalus and ventriculomegaly, currently lacks effective treatments. We discovered that meningeal lymphatics in mouse models of Down syndrome were incompletely developed and abnormally formed. Selective overexpression of Piezo1 in lymphatics or systemic administration of Yoda1 in mice with hydrocephalus or Down syndrome resulted in a notable decrease in pathological CSF accumulation, ventricular enlargement and other associated disease symptoms. Together, our study highlights the importance of Piezo1-mediated lymphatic mechanotransduction in maintaining brain fluid drainage and identifies Piezo1 as a promising therapeutic target for treating excessive CSF accumulation and ventricular enlargement.
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- News Mentions: 53
Included in
Cardiology Commons, Cardiovascular Diseases Commons, Neurology Commons, Neurosciences Commons, Urology Commons
