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dc.contributor.authorRosell-del-Valle, Cristina
dc.contributor.authorPedraza-Benítez, María del Carmen 
dc.contributor.authorManuel, Iván
dc.contributor.authorMoreno-Rodríguez, Marta
dc.contributor.authorRodríguez-Puertas, Rafael
dc.contributor.authorCastilla-Ortega, María Estela 
dc.contributor.authorCaramés-Tejedor, José María 
dc.contributor.authorGómez-Conde, Ana Isabel
dc.contributor.authorZambrana-Infantes, Emma
dc.contributor.authorOrtega-Pinazo, Jesús
dc.contributor.authorSerrano-Castro, Pedro Jesús 
dc.contributor.authorChun, Jerold
dc.contributor.authorRodriguez-de-Fonseca, Fernando
dc.contributor.authorSantín-Núñez, Luis Javier 
dc.contributor.authorEstivill-Torrús, Guillermo
dc.date.accessioned2022-03-16T11:53:07Z
dc.date.available2022-03-16T11:53:07Z
dc.date.issued2021-06-06
dc.identifier.urihttps://hdl.handle.net/10630/23857
dc.description.abstractSeveral studies have demonstrated that lysophosphatidic acid (LPA) acts through its LPA receptors in multiple biological and behavioral processes, including adult hippocampal neurogenesis, hippocampal-dependent memory, and emotional regulation. However, analyses of the effects have typically involved acute treatments, and there is no information available regarding the effect of the chronic pharmacological modulation of the LPA/LPA receptors-signaling pathway. Thus, we analyzed the effect of the chronic (21 days) and continuous intracerebroventricular (ICV) infusion of C18:1 LPA and the LPA1-3 receptor antagonist Ki16425 in behavior and adult hippocampal neurogenesis. Twenty-one days after continuous ICV infusions, mouse behaviors in the open field test, Y-maze test and forced swimming test were assessed. In addition, the hippocampus was examined for c-Fos expression and α-CaMKII and phospho-α-CaMKII levels. The current study demonstrates that chronic C18:1 LPA produced antidepressant effects, improved spatial working memory, and enhanced adult hippocampal neurogenesis. In contrast, chronic LPA1-3 receptor antagonism disrupted exploratory activity and spatial working memory, induced anxiety and depression-like behaviors and produced an impairment of hippocampal neurogenesis. While these effects were accompanied by an increase in neuronal activation in the DG of C18:1 LPA-treated mice, Ki16425-treated mice showed reduced neuronal activation in CA3 and CA1 hippocampal subfields. Treatment with the antagonist also induced an imbalance in the expression of basal/activated α-CaMKII protein forms. These outcomes indicate that the chronic central modulation of the LPA receptors-signaling pathway in the brain regulates cognition and emotion, likely comprising hippocampal-dependent mechanisms. The use of pharmacological modulation of this pathway in the brain may potentially be targeted for the treatment of several neuropsychiatric conditions.es_ES
dc.description.sponsorshipThis work was supported by grants from the Spanish Ministry of Science, Innovation and Universities, co-funded by the European Regional Development Fund (ERDF, EU), (PSI2017-82604R, to LJS; PSI2017-83408-P to CP; PI16/01510, to GET) and the Andalusian Regional Ministries of Economy, Knowledge, Business and University (CTS643 to GET) and of Health and Families (Nicolas Monardes Programme to GET). We gratefully acknowledge IBIMA joint support structures for research (ECAI) of Microscopy and Animal Experimentation for the immunohistology and maintenance of mice, respectively, as well as technical assistance. Technical and human support provided by the General Research Services SGIker [University of the Basque Country (UPV/EHU), Ministry of Science, Innovation and Universities, Basque Government, European Regional Development Fund (ERDF) and European Social Fund (ESF)] is gratefully acknowledged.es_ES
dc.language.isoenges_ES
dc.publisherProgress in Neuro-Psychopharmacology and Biological Psychiatryes_ES
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectHipocampo (Cerebro)es_ES
dc.subject.otherLysophosphatidic acid receptores_ES
dc.subject.otherEmotional behaviores_ES
dc.subject.otherWorking memoryes_ES
dc.subject.otherAdult hippocampal neurogenesises_ES
dc.subject.otherC-Foses_ES
dc.subject.otherα-CaMKIIes_ES
dc.titleChronic central modulation of LPA/LPA receptors-signaling pathway in the mouse brain regulates cognition, emotion, and hippocampal neurogenesis.es_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.centroFacultad de Psicología y Logopediaes_ES
dc.identifier.doihttps://doi.org/10.1016/j.pnpbp.2020.110156
dc.type.hasVersioninfo:eu-repo/semantics/submittedVersiones_ES


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