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Antidepressant low doses of ketamine and melatonin in combination produce additive neurogenesis in human olfactory neuronal precursors

dc.creatorEstrada-Reyes, Rosaes_ES
dc.creatorQuero-Chávez, Daniel B.es_ES
dc.creatorAlarcón-Elizalde, Salvadores_ES
dc.creatorCercós, Montserrat G.es_ES
dc.creatorCitlali Trueta, Citlalies_ES
dc.creatorConstantino-Jonapa, Luis A.es_ES
dc.creatorOikawa-Sala, Juliánes_ES
dc.creatorJesús Argueta, Jesúses_ES
dc.creatorCruz-Garduño, Ricardoes_ES
dc.creatorDubocovich, Margarita L.es_ES
dc.creatorBenítez-King, Gloria A.es_ES
dc.date2022
dc.date.accessioned2024-12-19T20:33:34Z
dc.date.available2024-12-19T20:33:34Z
dc.date.issued2022
dc.identifierJC28NC22es_ES
dc.identifier.urihttp://repositorio.inprf.gob.mx/handle/123456789/8175
dc.identifier.urihttps://doi.org/10.3390/molecules27175650
dc.descriptionMelatonin (MEL), an indolamine with diverse functions in the brain, has been shown to produce antidepressant-like effects, presumably through stimulating neurogenesis. We recently showed that the combination of MEL with ketamine (KET), an NMDA receptor antagonist, has robust antidepressant-like effects in mice, at doses that, by themselves, are non-effective and have no adverse effects. Here, we show that the KET/MEL combination increases neurogenesis in a clone derived from human olfactory neuronal precursors, a translational pre-clinical model for effects in the human CNS. Neurogenesis was assessed by the formation of cell clusters > 50 µm in diameter, positively stained for nestin, doublecortin, BrdU and Ki67, markers of progenitor cells, neurogenesis, and proliferation. FGF, EGF and BDNF growth factors increased the number of cell clusters in cultured, cloned ONPs. Similarly, KET or MEL increased the number of clusters in a dose-dependent manner. The KET/MEL combination further increased the formation of clusters, with a maximal effect obtained after a triple administration schedule. Our results show that the combination of KET/MEL, at subeffective doses that do not produce adverse effects, stimulate neurogenesis in human neuronal precursors. Moreover, the mechanism by which the combination elicits neurogenesis is meditated by melatonin receptors, CaM Kinase II and CaM antagonism. This could have clinical advantages for the fast treatment of depression.es_ES
dc.formatPDFes_ES
dc.language.isoenges_ES
dc.publisherMDPIes_ES
dc.relation27(17):5650
dc.rightsAcceso Cerradoes_ES
dc.titleAntidepressant low doses of ketamine and melatonin in combination produce additive neurogenesis in human olfactory neuronal precursorses_ES
dc.typeArtículoes_ES
dc.contributor.affiliationLaboratorio de Fitofarmacología, Dirección de Investigaciones en Neurociencias, Instituto Nacional Psiquiatría Ramón de la Fuente Muñiz, Calzada Mexico-Xochimilco 101, San Lorenzo Huipulco, Tlalpan, Ciudad de México 14370, Mexico
dc.contributor.emailbekin@imp.edu.mx; bekin54@hotmail.com
dc.relation.jnabreviadoMOLECULES
dc.relation.journalMolecules
dc.identifier.placeSuiza
dc.date.published2022
dc.identifier.organizacionInstituto Nacional de Psiquiatría Ramón de la Fuente Muñiz
dc.identifier.eissn1420-3049
dc.identifier.doi10.3390/molecules27175650
dc.subject.kwMelatonin
dc.subject.kwKetamine
dc.subject.kwNeurogenesis
dc.subject.kwOlfactory neuronal precursors
dc.subject.kwAntidepressants


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