Abstract
Ependymal cell cilia help move cerebrospinal fluid through the cerebral ventricles, but the regulation of their beat frequency remains unclear. Using in vitro, high-speed video microscopy and in vivo magnetic resonance imaging in mice, we found that the metabolic peptide melanin-concentrating hormone (MCH) positively controlled cilia beat frequency, specifically in the ventral third ventricle, whereas a lack of MCH receptor provoked a ventricular size increase.
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Acknowledgements
We thank J.M. Friedman (Rockefeller University) for Pmch-CFP mice, J. Boutin (Institut de Recherche Servier) for the MCHR1 antagonists, F. Kober and T. Troalen for cine phase-contrast MRI tests, A. Le Troter for assistance in three-dimensional reconstruction of brain MRI, C. Houdayer for laser-capture dissections, V. Thieffin for animal care, I. Larre for help with immunoassays, F. Aguila for artwork, J. Chabry and P. Mollard for discussions, G. Agarwal for help with Matlab, and S. Rasika and P. Haghighi for corrections and remarks on the manuscript. Supported by the Agence Nationale de la Recherche (ANR; ANR-08-MNPS-018-01 to J.-L.N., ANR Gliodiabesity project to V.P. and ANR-09-BLAN-0267 to V.P.), the CNRS Institut National des Sciences Biologiques (INSB), European Union 6th Framework Program STREPS/NEST-APES 28594 (J.L.N.), Projets Exploratoires Premier Soutien (INSB; A.G. and J.-L.N.), the Fondation de la Recherche Médicale (J.-L.N.), and postdoctoral fellowships from the ANR-08-MNPS-018-01 and CNRS (INSB) and awards from the Société Française de Nutrition 2011 and the Institut Danone 2012 (G.C.). A.A. was supported by the Douglas Foundation, McGill University, Canadian Fund for Innovation, Research Chair (Tier 2), and Institute for Health Research and the Natural Science and Engineering Council of Canada.
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G.C., F.B., A.V., F.L., B.D., V.P., L.L., C.R., P.M., S.H., P.-Y.R., A.P.-P. and A.G. performed the experiments. N.R. and O.M. engineered analytical tools. A.A. and B.L. engineered Mchr1−/− mice. G.C., A.V., V.P., T.L., R.C., P.-Y.R., J.-L.N. and A.G. analyzed the data. G.C., J.-L.N. and A.G. wrote the paper.
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Supplementary Text and Figures
Supplementary Figures 1–8 and Supplementary Table 1 (PDF 1370 kb)
Supplementary Movie 1
Representative video recording of the CBF of ciliated ependymal cells in the third ventricle. (AVI 1727 kb)
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Conductier, G., Brau, F., Viola, A. et al. Melanin-concentrating hormone regulates beat frequency of ependymal cilia and ventricular volume. Nat Neurosci 16, 845–847 (2013). https://doi.org/10.1038/nn.3401
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DOI: https://doi.org/10.1038/nn.3401