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Glial-restricted precursors stimulate endogenous cytogenesis and effectively recover emotional deficits in a model of cytogenesis ablation

2024-03-07Research article Open access
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dc.contributor.authorMartins-Macedo, Joana
dc.contributor.authorAraújo, Bruna
dc.contributor.authorAnjo, Sandra I.
dc.contributor.authorSilveira-Rosa, Tiago
dc.contributor.authorPatrício, Patrícia
dc.contributor.authorAlves, Nuno Dinis
dc.contributor.authorSilva, Joana M.
dc.contributor.authorTeixeira, Fábio G.
dc.contributor.authorManadas, Bruno
dc.contributor.authorRodrigues, Ana J.
dc.contributor.authorLepore, Angelo C.
dc.contributor.authorSalgado, António J.
dc.contributor.authorGomes, Eduardo D.
dc.contributor.authorPinto, Luísa
dc.contributor.authorGomes, Eduardo
dc.date.accessioned2025-10-21T10:17:02Z
dc.date.available2025-10-21T10:17:02Z
dc.date.issued2024-03-07
dc.description.abstractAdult cytogenesis, the continuous generation of newly-born neurons (neurogenesis) and glial cells (gliogenesis) throughout life, is highly impaired in several neuropsychiatric disorders, such as Major Depressive Disorder (MDD), impacting negatively on cognitive and emotional domains. Despite playing a critical role in brain homeostasis, the importance of gliogenesis has been overlooked, both in healthy and diseased states. To examine the role of newly formed glia, we transplanted Glial Restricted Precursors (GRPs) into the adult hippocampal dentate gyrus (DG), or injected their secreted factors (secretome), into a previously validated transgenic GFAP-tk rat line, in which cytogenesis is transiently compromised. We explored the long-term effects of both treatments on physiological and behavioral outcomes. Grafted GRPs reversed anxiety-like deficits and demonstrated an antidepressant-like effect, while the secretome promoted recovery of only anxiety-like behavior. Furthermore, GRPs elicited a recovery of neurogenic and gliogenic levels in the ventral DG, highlighting the unique involvement of these cells in the regulation of brain cytogenesis. Both GRPs and their secretome induced significant alterations in the DG proteome, directly influencing proteins and pathways related to cytogenesis, regulation of neural plasticity and neuronal development. With this work, we demonstrate a valuable and specific contribution of glial progenitors to normalizing gliogenic levels, rescuing neurogenesis and, importantly, promoting recovery of emotional deficits characteristic of disorders such as MDD.por
dc.identifier.citationMartins-Macedo, J., Araújo, B., Anjo, S. I., Silveira-Rosa, T., Patrício, P., Alves, N. D., Silva, J. M., Teixeira, F. G., Manadas, B., Rodrigues, A. J., Lepore, A. C., Salgado, A. J., Gomes, E. D., & Pinto, L. (2024). Glial-restricted precursors stimulate endogenous cytogenesis and effectively recover emotional deficits in a model of cytogenesis ablation. Molecular Psychiatry, 29(7), 2185–2198. https://doi.org/10.1038/s41380-024-02490-z
dc.identifier.doi10.1038/s41380-024-02490-z
dc.identifier.eissn1476-5578
dc.identifier.issn1359-4184
dc.identifier.urihttp://hdl.handle.net/10400.22/30656
dc.language.isoeng
dc.peerreviewedyes
dc.publisherSpringer Nature
dc.relation.hasversionhttps://www.nature.com/articles/s41380-024-02490-z
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectGlial-restricted precursors
dc.subjectStimulate endogenous cytogenesis
dc.titleGlial-restricted precursors stimulate endogenous cytogenesis and effectively recover emotional deficits in a model of cytogenesis ablationpor
dc.typeresearch article
dspace.entity.typePublication
oaire.citation.endPage2198
oaire.citation.startPage2185
oaire.citation.titleMolecular Psychiatry
oaire.citation.volume29
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameGomes
person.givenNameEduardo
person.identifier776948
person.identifier.ciencia-id7B13-B51D-97FF
person.identifier.orcid0000-0003-3179-1741
person.identifier.scopus-author-id55931679600
relation.isAuthorOfPublicationa4f4c0d1-5891-482a-a083-90a32e6ddc87
relation.isAuthorOfPublication.latestForDiscoverya4f4c0d1-5891-482a-a083-90a32e6ddc87

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