Agmatine, by Improving Neuroplasticity Markers and Inducing Nrf2, Prevents Corticosterone-Induced Depressive-Like Behavior in Mice

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dc.contributor.authorFreitas, Andiara E.
dc.contributor.authorNavarro González De Mesa, Elisa
dc.contributor.authorGarcía Lopez, Manuela
dc.date.accessioned2024-01-16T10:37:11Z
dc.date.available2024-01-16T10:37:11Z
dc.date.issued2015-05-13
dc.description.abstractAgmatine, an endogenous neuromodulator, is a potential candidate to constitute an adjuvant/monotherapy for the management of depression. A recent study by our group demonstrated that agmatine induces Nrf2 and protects against corticosterone effects in a hippocampal neuronal cell line. The present study is an extension of this previous study by assessing the antidepressant-like effect of agmatine in an animal model of depression induced by corticosterone in mice. Swiss mice were treated simultaneously with agmatine or imipramine at a dose of 0.1 mg/kg/day (p.o.) and corticosterone for 21 days and the daily administrations of experimental drugs were given immediately prior to corticosterone (20 mg/kg/day, p.o.) administrations. Wild-type C57BL/6 mice (Nrf2 (+/+)) and Nrf2 KO (Nrf2 (-/-)) were treated during 21 days with agmatine (0.1 mg/kg/day, p.o.) or vehicle. Twenty-four hours after the last treatments, the behavioral tests and biochemical assays were performed. Agmatine treatment for 21 days was able to abolish the corticosterone-induced depressive-like behavior and the alterations in the immunocontent of mature BDNF and synaptotagmin I, and in the serotonin and glutamate levels. Agmatine also abolished the corticosterone-induced changes in the morphology of astrocytes and microglia in CA1 region of hippocampus. In addition, agmatine treatment in control mice increased noradrenaline, serotonin, and dopamine levels, CREB phosphorylation, mature BDNF and synaptotagmin I immunocontents, and reduced pro-BDNF immunocontent in the hippocampus. Agmatine's ability to produce an antidepressant-like effect was abolished in Nrf2 (-/-) mice. The present results reinforce the participation of Nrf2 in the antidepressant-like effect produced by agmatine and expand literature data concerning its mechanisms of action.
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Medicina
dc.description.refereedTRUE
dc.description.statuspub
dc.identifier.citationFreitas AE, Egea J, Buendia I, Gómez-Rangel V, Parada E, Navarro E, Casas AI, Wojnicz A, Ortiz JA, Cuadrado A, Ruiz-Nuño A, Rodrigues ALS, Lopez MG. Agmatine, by Improving Neuroplasticity Markers and Inducing Nrf2, Prevents Corticosterone-Induced Depressive-Like Behavior in Mice. Mol Neurobiol. 2016 Jul;53(5):3030-3045. doi: 10.1007/s12035-015-9182-6
dc.identifier.doi10.1007/s12035-015-9182-6
dc.identifier.issn0893-7648
dc.identifier.issn1559-1182
dc.identifier.officialurlhttps://link.springer.com/article/10.1007/s12035-015-9182-6
dc.identifier.relatedurlhttps://pubmed.ncbi.nlm.nih.gov/25966970/
dc.identifier.urihttps://hdl.handle.net/20.500.14352/93308
dc.journal.titleMolecular Neurobiology
dc.language.isoeng
dc.page.final3045
dc.page.initial3030
dc.publisherSpringer
dc.rights.accessRightsrestricted access
dc.subject.cdu577.2
dc.subject.keywordAgmatine
dc.subject.keywordBDNF
dc.subject.keywordCorticosterone
dc.subject.keywordDepression
dc.subject.keywordNrf2
dc.subject.ucmCiencias Biomédicas
dc.subject.unesco24 Ciencias de la Vida
dc.titleAgmatine, by Improving Neuroplasticity Markers and Inducing Nrf2, Prevents Corticosterone-Induced Depressive-Like Behavior in Mice
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number53
dspace.entity.typePublication
relation.isAuthorOfPublicationd0e22d4d-2011-4a9f-bd9c-609855dba391
relation.isAuthorOfPublication.latestForDiscoveryd0e22d4d-2011-4a9f-bd9c-609855dba391
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