{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:37:51Z","timestamp":1790660271691,"version":"4.1.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T00:00:00Z","timestamp":1559779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"crossref","award":["PICT 2013-2772"],"award-info":[{"award-number":["PICT 2013-2772"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005363","name":"Universidad de Buenos Aires","doi-asserted-by":"publisher","award":["20020160100050BA"],"award-info":[{"award-number":["20020160100050BA"]}],"id":[{"id":"10.13039\/501100005363","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","doi-asserted-by":"crossref","award":["PIP0567"],"award-info":[{"award-number":["PIP0567"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Multiple sclerosis (MS) is an immune-mediated central nervous system disease mostly affecting young people. Multiple sclerosis and other neurodegenerative and white matter disorders involve oligodendrocyte (OL) damage and demyelination. Therefore, elucidating the signaling pathways involved in the remyelination process through the maturation of OL progenitor cells (OPCs) may contribute to the development of new therapeutic approaches. In this context, this paper further characterizes toxic cuprizone (CPZ)-induced demyelination and spontaneous remyelination in rats and investigates the role of ligand-dependent Notch signaling activation along demyelination\/remyelination both in vivo and in vitro. Toxic treatment generated an inflammatory response characterized by both microgliosis and astrogliosis. Interestingly, early demyelination revealed an increase in the proportion of Jagged1+\/GFAP+ cells, which correlated with an increase in Jagged1 transcript and concomitant Jagged1-driven Notch signaling activation, particularly in NG2+ OPCs, in both the corpus callosum (CC) and subventricular zone (SVZ). The onset of remyelination then exhibited an increase in the proportion of F3\/contactin+\/NG2+ cells, which correlated with an increase in F3\/contactin transcript during ongoing remyelination in the CC. Moreover, neurosphere cultures revealed that neural progenitor cells present in the brain SVZ of CPZ-treated rats recapitulate in vitro the mechanisms underlying the response to toxic injury observed in vivo, compensating for mature OL loss. Altogether, the present results offer strong evidence of cell-type and ligand-specific Notch signaling activation and its time- and area-dependent participation in toxic demyelination and spontaneous remyelination.<\/jats:p>","DOI":"10.1093\/toxsci\/kfz130","type":"journal-article","created":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T03:23:08Z","timestamp":1559359388000},"page":"172-192","source":"Crossref","is-referenced-by-count":28,"title":["Demyelination-remyelination in the Central Nervous System: Ligand-dependent Participation of the Notch Signaling Pathway"],"prefix":"10.1093","volume":"171","author":[{"given":"Patricia A","family":"Mathieu","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Farmacia y Bioqu\u00edmica, Instituto de Qu\u00edmica y Fisicoqu\u00edmica Biol\u00f3gicas (IQUIFIB, UBA-CONICET)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda F","family":"Almeira Gubiani","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Farmacia y Bioqu\u00edmica, Instituto de Qu\u00edmica y Fisicoqu\u00edmica Biol\u00f3gicas (IQUIFIB, UBA-CONICET)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9bora","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Farmacia y Bioqu\u00edmica, Instituto de Qu\u00edmica y Fisicoqu\u00edmica Biol\u00f3gicas (IQUIFIB, UBA-CONICET)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura I","family":"G\u00f3mez Pinto","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Farmacia y Bioqu\u00edmica, Instituto de Qu\u00edmica y Fisicoqu\u00edmica Biol\u00f3gicas (IQUIFIB, UBA-CONICET)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda de Luj\u00e1n","family":"Calcagno","sequence":"additional","affiliation":[{"name":"Departamento de Fisicomatem\u00e1tica, Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, C1113AAD Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M","family":"Adamo","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Farmacia y Bioqu\u00edmica, Instituto de Qu\u00edmica y Fisicoqu\u00edmica Biol\u00f3gicas (IQUIFIB, UBA-CONICET)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,6,6]]},"reference":[{"key":"2019091012183272100_kfz130-B1","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.expneurol.2005.12.027","article-title":"Remyelination after cuprizone-induced demyelination in the rat is stimulated by apotransferrin","volume":"198","author":"Adamo","year":"2006","journal-title":"Exp. 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