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dc.contributor.authorDiaz-Aparicio, Irune
dc.contributor.authorParis, Iñaki
dc.contributor.authorSierra‐Torre, Virginia
dc.contributor.authorPlaza‐Zabala, Ainhoa
dc.contributor.authorRodríguez-Iglesias, Noelia
dc.contributor.authorMárquez-Ropero, Mar
dc.contributor.authorBeccari, Sol
dc.contributor.authorHuguet, Paloma
dc.contributor.authorAbiega, Oihane
dc.contributor.authorAlberdi, Elena
dc.contributor.authorMatute, Carlos
dc.contributor.authorBernales, Irantzu
dc.contributor.authorSchulz, Angela
dc.contributor.authorOtrokocsi, Lilla
dc.contributor.authorSperlagh, Beata
dc.contributor.authorHapponen, Kaisa E.
dc.contributor.authorLemke, Greg
dc.contributor.authorMaletic-Savatic, Mirjana
dc.contributor.authorValero, Jorge
dc.contributor.authorSierra, Amanda
dc.date.accessioned2024-01-25T09:25:10Z
dc.date.available2024-01-25T09:25:10Z
dc.date.issued2020-02-12
dc.identifier.issn0270-6474
dc.identifier.urihttp://hdl.handle.net/10366/154668
dc.description.abstractDuring adult hippocampal neurogenesis, most newborn cells undergo apoptosis and are rapidly phagocytosed by resident microglia to prevent the spillover of intracellular contents. Here, we propose that phagocytosis is not merely passive corpse removal but has an active role in maintaining neurogenesis. First, we found that neurogenesis was disrupted in male and female mice chronically deficient for two phagocytosis pathways: the purinergic receptor P2Y12, and the tyrosine kinases of the TAM family Mer tyrosine kinase (MerTK)/Axl. In contrast, neurogenesis was transiently increased in mice in which MerTK expression was conditionally downregulated. Next, we per-formed a transcriptomic analysis of the changes induced by phagocytosis in microglia in vitro and identified genes involved in metabolism, chromatin remodeling, and neurogenesis-related functions. Finally, we discovered that the secretome of phagocytic microglia limits the production of new neurons both in vivo and in vitro. Our data suggest that microglia act as a sensor of local cell death, modulating the balance between proliferation and survival in the neurogenic niche through the phagocytosis secretome, thereby supporting the long-term maintenance of adult hippocampal neurogenesis.es_ES
dc.description.sponsorshipThis work was supported by grants from the Spanish Ministry of Economy and Competitiveness (http://www. mineco.gob.es) with FEDER funds to A.S. (BFU2012-32089 and RYC-2013-12817) to A.S. and J.V. (BFU2015-66689); a Leonardo Award from the BBVA Foundation to A.S. (IN16,_BBM_BAS_0260); a Basque Government Department of Education project to A.S. (PI_2016_1_0011; http://www.euskadi.eus/basque-government/department-educa- tion/); Ikerbasque start-up funds to J.V.; a Hungarian Research and Development Fund Grant (K116654) to B.S.; a Hungarian Brain Research Program Grant (2017-1.2.1-NKP-2017-00002) to B.S.; a National Institutes of Health Grant (AG060748) to G.L.es_ES
dc.language.isoenges_ES
dc.subjectadult neurogenesises_ES
dc.subjectMerTK/Axles_ES
dc.subjectmicrogliaes_ES
dc.subjectP2Y12es_ES
dc.subjectphagocytosises_ES
dc.subjectsecretomees_ES
dc.titleMicroglia Actively Remodel Adult Hippocampal Neurogenesis through the Phagocytosis Secretomees_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.relation.publishversionhttps://doi.org/10.1523/JNEUROSCI.0993-19.2019
dc.subject.unesco2490 Neurociencias
dc.subject.unesco2410 Biología Humana
dc.identifier.doi10.1523/JNEUROSCI.0993-19.2019
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES
dc.identifier.essn1529-2401
dc.journal.titleThe Journal of Neurosciencees_ES
dc.volume.number40es_ES
dc.issue.number7es_ES
dc.page.initial1453es_ES
dc.page.final1482es_ES
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersiones_ES


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