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Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluid

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dc.contributor.author Drieu, Antoine
dc.contributor.author Du, Siling
dc.contributor.author Storck, Steffen E.
dc.contributor.author Rustenhoven, Justin
dc.contributor.author Papadopoulos, Zachary
dc.contributor.author Dykstra, Taitea
dc.contributor.author Zhong, Fenghe
dc.contributor.author Kim, Kyungdeok
dc.contributor.author Blackburn, Susan
dc.contributor.author Mamuladze, Tornike
dc.contributor.author Harari, Oscar
dc.contributor.author Karch, Celeste M.
dc.contributor.author Bateman, Randall J.
dc.contributor.author Perrin, Richard J.
dc.contributor.author Farlow, Martin R.
dc.contributor.author Chhatwal, Jasmeer P.
dc.contributor.author Dominantly Inherited Alzheimer Network
dc.contributor.author Hu, Song
dc.contributor.author Randolph, Gwendalyn J.
dc.contributor.author Allegri, Ricardo Francisco
dc.date.accessioned 2023-01-09T11:13:51Z
dc.date.available 2023-01-09T11:13:51Z
dc.date.issued 2022-11
dc.identifier.citation Drieu A, Du S, Storck SE, Rustenhoven J, Papadopoulos Z, Dykstra T, Zhong F, Kim K, Blackburn S, Mamuladze T, Harari O, Karch CM, Bateman RJ, Perrin RJ, Farlow MR, Chhatwal J; Dominantly Inherited Alzheimer Network; Hu S, Randolph GJ, Smirnov I, Kipnis J. Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluid. Nature. 2022 Nov;611(7936):585-593. doi: 10.1038/s41586-022-05397-3. Epub 2022 Nov 9. es_ES
dc.identifier.uri https://doi.org/10.1038/s41586-022-05397-3
dc.identifier.uri https://repositorio.fleni.org.ar/xmlui/handle/123456789/764
dc.description.abstract Macrophages are important players in the maintenance of tissue homeostasis1. Perivascular and leptomeningeal macrophages reside near the central nervous system (CNS) parenchyma2, and their role in CNS physiology has not been sufficiently well studied. Given their continuous interaction with the cerebrospinal fluid (CSF) and strategic positioning, we refer to these cells collectively as parenchymal border macrophages (PBMs). Here we demonstrate that PBMs regulate CSF flow dynamics. We identify a subpopulation of PBMs that express high levels of CD163 and LYVE1 (scavenger receptor proteins), closely associated with the brain arterial tree, and show that LYVE1+ PBMs regulate arterial motion that drives CSF flow. Pharmacological or genetic depletion of PBMs led to accumulation of extracellular matrix proteins, obstructing CSF access to perivascular spaces and impairing CNS perfusion and clearance. Ageing-associated alterations in PBMs and impairment of CSF dynamics were restored after intracisternal injection of macrophage colony-stimulating factor. Single-nucleus RNA sequencing data obtained from patients with Alzheimer's disease (AD) and from non-AD individuals point to changes in phagocytosis, endocytosis and interferon-γ signalling on PBMs, pathways that are corroborated in a mouse model of AD. Collectively, our results identify PBMs as new cellular regulators of CSF flow dynamics, which could be targeted pharmacologically to alleviate brain clearance deficits associated with ageing and AD. es_ES
dc.language.iso eng es_ES
dc.publisher Nature Publishing Group es_ES
dc.rights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by/2.5/ar/
dc.subject Cerebrospinal Fluid es_ES
dc.subject Líquido Cefalorraquídeo es_ES
dc.subject Alzheimer Disease es_ES
dc.subject Enfermedad de Alzheimer es_ES
dc.title Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluid es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.type info:eu-repo/semantics/publishedVersion
dc.description.fil Fil: Allegri, Ricardo Francisco. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.
dc.description.fil Fil: Drieu, Antoine. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Du, Siling. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Storck, Steffen E. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Rustenhoven, Justin. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Papadopoulos, Zachary. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Dykstra, Taitea. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Zhong, Fenghe. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Kim, Kyungdeok. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Blackburn, Susan. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Mamuladze, Tornike. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Harari, Oscar. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Karch, Celeste M. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Bateman, Randall J. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Perrin, Richard J. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Farlow, Martin R. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Chhatwal, Jasmeer. Harvard Medical School; Estados Unidos.
dc.description.fil Fil: Hu, Song. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Randolph, Gwendalyn J. Washington University in St Louis; Estados Unidos.
dc.relation.ispartofVOLUME 611
dc.relation.ispartofNUMBER 7936
dc.relation.ispartofPAGINATION 585-593.
dc.relation.ispartofCITY Basingstoke
dc.relation.ispartofCITY Reino Unido
dc.relation.ispartofISSN 1476-4687
dc.type.snrd info:ar-repo/semantics/artículo es_ES


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