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Knockdown of MLC1 in primary astrocytes causes cell vacuolation: A MLC disease cell model
- Source :
- Duarri, A, de Heredia, M L, Capdevila-Nortes, X, Ridder, M C, Montolio, M, Lopez-Hernandez, T, Boor, P K I, Lien, C F, Hagemann, T, Messing, A, Gorecki, D C, Scheper, G C, Martinez, A, Nunes, V, van der Knaap, M S & Estevez, R 2011, ' Knockdown of MLC1 in primary astrocytes causes cell vacuolation: A MLC disease cell model ', Neurobiology of Disease, vol. 43, no. 1, pp. 228-238 . https://doi.org/10.1016/j.nbd.2011.03.015, Recercat. Dipósit de la Recerca de Catalunya, instname, Neurobiology of Disease, 43(1), 228-238. Academic Press Inc., Dipòsit Digital de la UB, Universidad de Barcelona, Neurobiology of Disease, Vol 43, Iss 1, Pp 228-238 (2011), Neurobiology of disease, 43(1), 228-238. Academic Press Inc.
- Publication Year :
- 2011
-
Abstract
- Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of leukodystrophy, in the majority of cases caused by mutations in the MLC1 gene. MRI from MLC patients shows diffuse cerebral white matter signal abnormality and swelling, with evidence of increased water content. Histopathology in a MLC patient shows vacuolation of myelin, which causes the cerebral white matter swelling. MLC1 protein is expressed in astrocytic processes that are part of blood- and cerebrospinal fluid-brain barriers. We aimed to create an astrocyte cell model of MLC disease. The characterization of rat astrocyte cultures revealed MLC1 localization in cell-cell contacts, which contains other proteins described typically in tight and adherent junctions. MLC1 localization in these contacts was demonstrated to depend on the actin cytoskeleton: it was not altered when disrupting the microtubule or the GFAP networks. In human tissues, MLC1 and the protein Zonula Occludens 1 (ZO-1), which is linked to the actin cytoskeleton, co-localized by EM immunostaining and were specifically co-immunoprecipitated. To create an MLC cell model, knockdown of MLC1 in primary astrocytes was performed. Reduction of MLC1 expression resulted in the appearance of intracellular vacuoles. This vacuolation was reversed by the co-expression of human MLC1. Re-examination of a human brain biopsy from an MLC patient revealed that vacuoles were also consistently present in astrocytic processes. Thus, vacuolation of astrocytes is also a hallmark of MLC disease. (C) 2011 Elsevier Inc. All rights reserved.
- Subjects :
- Junctions
Pathology
medicine.medical_specialty
Adolescent
Down-Regulation
Astròcits
Neurophysiology
macromolecular substances
Biology
Article
lcsh:RC321-571
Rats, Sprague-Dawley
Mice
Myelin
Microtubule
Neurofisiologia
medicine
Animals
Humans
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Cells, Cultured
Volume
Cysts
Leukodystrophy
Membrane Proteins
Extracellular Fluid
Human brain
medicine.disease
Actin cytoskeleton
Rats
Hereditary Central Nervous System Demyelinating Diseases
medicine.anatomical_structure
Neurology
Astrocytes
Vacuoles
Astrocyte
Intracellular
Immunostaining
Subjects
Details
- Language :
- English
- ISSN :
- 09699961
- Database :
- OpenAIRE
- Journal :
- Duarri, A, de Heredia, M L, Capdevila-Nortes, X, Ridder, M C, Montolio, M, Lopez-Hernandez, T, Boor, P K I, Lien, C F, Hagemann, T, Messing, A, Gorecki, D C, Scheper, G C, Martinez, A, Nunes, V, van der Knaap, M S & Estevez, R 2011, ' Knockdown of MLC1 in primary astrocytes causes cell vacuolation: A MLC disease cell model ', Neurobiology of Disease, vol. 43, no. 1, pp. 228-238 . https://doi.org/10.1016/j.nbd.2011.03.015, Recercat. Dipósit de la Recerca de Catalunya, instname, Neurobiology of Disease, 43(1), 228-238. Academic Press Inc., Dipòsit Digital de la UB, Universidad de Barcelona, Neurobiology of Disease, Vol 43, Iss 1, Pp 228-238 (2011), Neurobiology of disease, 43(1), 228-238. Academic Press Inc.
- Accession number :
- edsair.doi.dedup.....bc1dd6bb0681d20c6429b0e563ddaf95