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Artículo

Galectin-3 controls the response of microglial cells to limit cuprizone-induced demyelination

Hoyos, Hernán CarlosIcon ; Rinaldi, MarianaIcon ; Mendez Huergo, Santiago PatricioIcon ; Marder, Nora MarielIcon ; Rabinovich, Gabriel AdriánIcon ; Pasquini, Juana MariaIcon ; Pasquini, Laura AndreaIcon
Fecha de publicación: 02/2014
Editorial: Elsevier
Revista: Neurobiology of Disease
ISSN: 0969-9961
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Neurociencias; Neurología Clínica

Resumen

Galectin-3 (Gal-3) is a β-galactoside-binding lectin that plays an important role in inflammatory and neurodegenerative diseases. Cuprizone (CPZ)-induced demyelination is characterized by the loss of mature oligodendrocytes (OLG) by apoptosis, myelin sheath degeneration and recruitment of microglia and astrocytes to the lesioned area. We compared CPZ-induced demyelination of 8-week-old Lgals3(-/-) vs WT mice. Lgals3(-/-) mice displayed a similar susceptibility to CPZ-induced demyelination up to the fifth week, as evaluated by MBP immunostaining and electronic microscopy. However, OLG progenitors (OPC) generated in CPZ-treated Lgals3(-/-) mice showed diminished arborization, suggesting decreased ability of these cells to differentiate. Surprisingly, while WT mice experienced spontaneous remyelination in the fifth week of CPZ treatment-even though the CPZ diet was maintained up to sixth week-Lgals3(-/-) mice lacked this capacity and suffered continuous demyelination up to the sixth week, accompanied by pronounced astroglial activation. Moreover, after 2weeks of CPZ treatment, WT and Lgals3(-/-) mice showed lower innate anxiety as compared with respective naive mice, but only CPZ-treated Lgals3(-/-) mice showed decreased locomotor activity and exhibited spatial working memory impairment. Expression of Gal-3 increased during CPZ-induced demyelination in microglia but not in astrocytes. While CPZ-treated WT mice displayed heightened microglial activation associated with ED1 expression and pronounced upregulation of the phagocytic receptor TREM-2b, this effect was not observed in CPZ-treated Lgals3(-/-) mice which, in spite of showing an increased number of microglia, these cells evidenced caspase-3 activation. Our results indicate that Gal-3 is expressed in microglial cells to modulate their phenotype, facilitating the onset of remyelination and OLG differentiation.
Palabras clave: Galectina 3 , Desmielinización , Cuprizona , Fenotipo Microglial , Diferenciación Oligodendroglial , Trem 2b
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Atribución-NoComercial-SinDerivadas 2.5 Argentina (CC BY-NC-ND 2.5 AR)
Identificadores
URI: http://hdl.handle.net/11336/6587
URL: http://www.sciencedirect.com/science/article/pii/S0969996113002982
DOI: http://dx.doi.org/10.1016/j.nbd.2013.10.023
Colecciones
Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos(IQUIFIB)
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Articulos(OCA CIUDAD UNIVERSITARIA)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA CIUDAD UNIVERSITARIA
Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Citación
Hoyos, Hernán Carlos; Rinaldi, Mariana; Mendez Huergo, Santiago Patricio; Marder, Nora Mariel; Rabinovich, Gabriel Adrián; et al.; Galectin-3 controls the response of microglial cells to limit cuprizone-induced demyelination; Elsevier; Neurobiology of Disease; 62; 2-2014; 441-455
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