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dc.contributor.authorCipriani, Raffaela
dc.contributor.authorChara Ventura, Juan Carlos
dc.contributor.authorRodríguez-Antigüedad Zarranz, Alfredo
dc.contributor.authorMatute Almau, Carlos José
dc.date.accessioned2018-04-09T08:47:45Z
dc.date.available2018-04-09T08:47:45Z
dc.date.issued2017-07-24
dc.identifier.citationJournal of Neuroinflammation 14: (2017) // Article ID 147es_ES
dc.identifier.issn1742-2094
dc.identifier.urihttp://hdl.handle.net/10810/26167
dc.description.abstractBackground: FTY720 (fingolimod, Gilenya (TM)) is an oral, blood-brain barrier (BBB)-passing drug approved as immunomodulatory treatment for relapsing-remitting form of the multiple sclerosis (MS). In addition, FTY720 exerts several effects in the central nervous system (CNS), ranging from neuroprotection to reduction of neuroinflammation. However, the neurogenic and oligodendrogenic potential of FTY720 has been poorly investigated. In this study, we assessed the effect of FTY720 on the production of new neurons and oligodendrocytes from neural stem/precursor cells both in vitro and in vivo. Methods: Neural stem cells (NSCs) derived from the young rat subventricular zone (SVZ) were exposed to FTY720 (10, 100 nM), and their differentiation into neurons and oligodendrocytes was measured using immunofluorescence for anti-beta-III tubulin or CNPase (2',3'-cyclic nucleotide 3'-phosphodiesterase) as markers of mature neurons or oligodendrocytes, respectively. In addition, intracerebroventricular (icv) administration of kainic acid (KA; 0.5 mu g/2 mu l) in Sprague-Dawley rats was used as an in vivo model of neuronal death and inflammation. FTY720 was applied icv (1 mu g/2 mu l), together with KA, plus intraperitoneally (ip; 1 mg/kg) 24 h before, and daily, until sacrifice 8 days after KA injection. To visualize cell proliferation in the hippocampus and in white matter regions, rats were administered 5-bromo-2-deoxyuridine (BrdU) 100 mg/kg, ip injected every 2 days. Immunohistochemical analyses were performed on rat brain slices to measure the production of new neuronal precursors (doublecortin/DCX+ cells) and new oligodendrocytes precursors (proteoglycan/NG2(+) cells). Results: In this study, we observed that FTY720 increased postnatal NSCs differentiation into both neurons and oligodendrocytes in vitro. In turn, in adult animals, FTY720 enhanced the percentage of BrdU(+) cells coexpressing DCX marker, both in basal (FTY720 alone) and in neurodegenerative (FTY720 + KA) conditions. However, FTY720 had only a partial effect on proliferation and differentiation of oligodendrocyte progenitor cell (OPC) population in vivo. Conclusions: FTY720 promotes neurogenesis and oligodendrogenesis in vitro under basal conditions. In addition, it increases the generation of neuroblasts and oligodendrocytes after excitotoxic brain injury. This suggests that FTY720 has the potential to activate the neurogenic niche and thus favour tissue repair after lesion.es_ES
dc.description.sponsorshipThis study was supported by the Novartis Farmaceutica SA, Ministerio de Economia y Competitividad (MINECO) and Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED). RC was funded by Novartis Farmaceutica SA.es_ES
dc.language.isoenges_ES
dc.publisherBiomed Centrales_ES
dc.relationinfo:eu-repo/grantAgreement/MINECO/es_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.subjectFTY720es_ES
dc.subjectneural stem cellses_ES
dc.subjectneurogenesises_ES
dc.subjectoligodendrocyte progenitor cellses_ES
dc.subjectdoublecortines_ES
dc.subjectNG2es_ES
dc.subjectkainic acides_ES
dc.subjecttemporal-lobe epilepsyes_ES
dc.subjectadult-mouse hippocampuses_ES
dc.subjectcentral-nervous-systemes_ES
dc.subjectstatus epilepticuses_ES
dc.subjectfingolimod FTY720es_ES
dc.subjectprogenitor cellses_ES
dc.subjectrat hippocampuses_ES
dc.subjectoligodendrocyte progenitorses_ES
dc.subjectinduced demyelinationes_ES
dc.titleEffects of FTY720 on brain neurogenic niches in vitro and after kainic acid-induced injuryes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.holder© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.es_ES
dc.rights.holderAtribución 3.0 España*
dc.relation.publisherversionhttps://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-017-0922-6es_ES
dc.identifier.doi10.1186/s12974-017-0922-6
dc.departamentoesNeurocienciases_ES
dc.departamentoeuNeurozientziakes_ES


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© The Author(s). 2017
Open Access
This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Except where otherwise noted, this item's license is described as © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.