Abstract
Astrocytes, the most abundant glial cells of the central nervous system are morphologically complex. They display numerous processes interacting with synapses and blood vessels. At the vascular interface, astrocyte endfeet-terminated processes almost entirely cover the blood vessel surface and participate to the gliovascular unit where important vascular properties of the brain are set such as the blood-brain barrier (BBB) integrity. How specific morphological and functional interactions between astrocytes and the vascular compartment develop has not been fully investigated. Here, we elaborated an original experimental strategy to study the postnatal development of astrocyte perivascular endfeet. Using purified gliovascular units, we focused on the postnatal expression of MLC1 and GlialCAM, two transmembrane proteins forming a complex enriched at the junction between mature astrocyte perivascular endfeet. We showed that MLC1 and GlialCAM were enriched and assembled into mature complexes in astrocyte perivascular endfeet between postnatal days 10 and 15, after the formation of astrocyte perivascular Aquaporin 4 water channels. These events correlated with the increased expression of Claudin-5 and P-gP, two endothelial-specific BBB components. These results illustrate for the first time that astrocyte perivascular endfeet differentiation is a complex and progressive process which correlates with BBB maturation. Moreover, our results suggest that maturation of the astrocyte endfeet MLC1/GlialCAM complex between postnatal days 10 and 15 might be a key event in the gliovascular unit maturation.
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Acknowledgments
This work has been financed by FRM “Fondation pour la recherche médicale” (PLP20170939025p60 to AG, AJE20171039094 to MCS and SPF20150934067 to ACB), “Fondation Maladies Rares” to MCS, “Contrat de Plan Etat-Région (CPER) Ile-de-France” to MCS, the European Leukodystrophies Association (ELA) Research Foundation (ELA2012-014C2B to RE), the Spanish Ministerio de Ciencia e Innovación (MICINN) (SAF2015-70377 to RE), the Generalitat de Catalunya (SGR2014-1178 to RE). RE is a recipient of an ICREA Academia prize. We thank Anna Capano for technical help and Philippe Mailly for help in image analysis. We are grateful to Xavier Declèves and Jean-Louis Laplanche for helpful discussions and constant support.
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MC-S and A-CB designed research; AG and A-CB performed research; AG, MC-S and A-CB analyzed data; XEV and RE provided resources; A-CB and MC-S wrote the paper.
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Gilbert, A., Vidal, X.E., Estevez, R. et al. Postnatal development of the astrocyte perivascular MLC1/GlialCAM complex defines a temporal window for the gliovascular unit maturation. Brain Struct Funct 224, 1267–1278 (2019). https://doi.org/10.1007/s00429-019-01832-w
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DOI: https://doi.org/10.1007/s00429-019-01832-w