Megalencephalic leukoencephalopathy with subcortical cysts is a developmental disorder of the gliovascular unit

Absence of the astrocyte-specific membrane protein MLC1 is responsible for megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare type of leukodystrophy characterized by early-onset macrocephaly and progressive white matter vacuolation that lead to ataxia, spasticity, and cognitive...

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Detalhes bibliográficos
Autores: Gilbert, Alice, Elorza Vidal, Xabier, Rancillac, Armelle, Chagnot, Audrey, Yetim, Mervé, Hingot, Vincent, Deffieux, Thomas, Boulay, Anne Cécile, Alvear Perez, Rodrigo, Cisternino, Salvatore, Martin, Sabrina, Taïb, Sonia, Gelot, Aontoinette, Mignon, Virginie, Favier, Maryline, Brunet, Isabelle, Declèves, Xavier, Tanter, Mickael, Estévez Povedano, Raúl, Vivien, Denis, Saubaméa, Bruno, Cohen Salmon, Martine
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2021
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/181715
Acesso em linha:https://hdl.handle.net/2445/181715
Access Level:Acceso aberto
Palavra-chave:Malalties del sistema nerviós central
Malalties rares
Astròcits
Central nervous system diseases
Rare diseases
Astrocytes
Descrição
Resumo:Absence of the astrocyte-specific membrane protein MLC1 is responsible for megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare type of leukodystrophy characterized by early-onset macrocephaly and progressive white matter vacuolation that lead to ataxia, spasticity, and cognitive decline. During postnatal development (from P5 to P15 in the mouse), MLC1 forms a membrane complex with GlialCAM (another astrocytic transmembrane protein) at the junctions between perivascular astrocytic processes. Perivascular astrocytic processes along with blood vessels form the gliovascular unit. It was not previously known how MLC1 influences the physiology of the gliovascular unit. Here, using the Mlc1 knock-out mouse model of MLC, we demonstrated that MLC1 controls the postnatal development and organization of perivascular astrocytic processes, vascular smooth muscle cell contractility, neurovascular coupling, and intraparenchymal interstitial fluid clearance. Our data suggest that MLC is a developmental disorder of the gliovascular unit, and perivascular astrocytic processes and vascular smooth muscle cell maturation defects are primary events in the pathogenesis of MLC and therapeutic targets for this disease.

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