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The ROCK inhibitor fasudil prevents chronic restraint stress-induced depressive-like behaviors and dendritic spine loss in rat hippocampus

dc.contributor.authorAliaga-Rojas, Esteban
dc.contributor.authorGarcía-Rojo, Gonzalo
dc.contributor.authorFresno, Cristóbal
dc.contributor.authorVilches, Natalia
dc.contributor.authorMora, Sergio
dc.contributor.authorTejos, Macarena
dc.contributor.authorDíaz-Véliz, Gabriela
dc.contributor.authorAguayo, Felipe I.
dc.contributor.authorFiedler, Jenny L.
dc.contributor.authorParra, Claudio S.
dc.contributor.authorParra-Fiedler, Nicolás
dc.contributor.authorRojas, Paulina S.
dc.contributor.authorPacheco, Aníbal
dc.date.accessioned2017-11-30T17:30:52Z
dc.date.available2017-11-30T17:30:52Z
dc.date.issued2017
dc.identifier.urihttp://repositorio.ucm.cl/handle/ucm/1512
dc.description.abstractBackground: Dendritic arbor simplification and dendritic spine loss in the hippocampus, a limbic structure implicated in mood disorders, are assumed to contribute to symptoms of depression. These morphological changes imply modifications in dendritic cytoskeleton. Rho GTPases are regulators of actin dynamics through their effector Rho kinase. We have reported that chronic stress promotes depressive-like behaviors in rats along with dendritic spine loss in apical dendrites of hippocampal pyramidal neurons, changes associated with Rho kinase activation. The present study proposes that the Rho kinase inhibitor Fasudil may prevent the stress-induced behavior and dendritic spine loss. Methods: Adult male Sprague-Dawley rats were injected with saline or Fasudil (i.p., 10 mg/kg) starting 4 days prior to and maintained during the restraint stress procedure (2.5 h/d for 14 days). Nonstressed control animals were injected with saline or Fasudil for 18 days. At 24 hours after treatment, forced swimming test, Golgi-staining, and immuno-western blot were performed. Results: Fasudil prevented stress-induced immobility observed in the forced swimming test. On the other hand, Fasudiltreated control animals showed behavioral patterns similar to those of saline-treated controls. Furthermore, we observed that stress induced an increase in the phosphorylation of MYPT1 in the hippocampus, an exclusive target of Rho kinase. This change was accompanied by dendritic spine loss of apical dendrites of pyramidal hippocampal neurons. Interestingly, increased pMYPT1 levels and spine loss were both prevented by Fasudil administration.es_CL
dc.language.isoenes_CL
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/*
dc.sourceInternational Journal of Neuropsychopharmacology, 20(4), 336–345es_CL
dc.subjectBehaviores_CL
dc.subjectDendritic spineses_CL
dc.subjectAntidepressantses_CL
dc.subjectROCK inhibitor Fasudiles_CL
dc.subjectStresses_CL
dc.titleThe ROCK inhibitor fasudil prevents chronic restraint stress-induced depressive-like behaviors and dendritic spine loss in rat hippocampuses_CL
dc.typeArticlees_CL
dc.ucm.facultadFacultad de Ciencias de la Saludes_CL
dc.ucm.indexacionScopuses_CL
dc.ucm.indexacionIsies_CL
dc.ucm.urisibib2.ucm.cl:2048/login?url=https://academic.oup.com/ijnp/article/20/4/336/2632175es_CL
dc.ucm.doidoi.org/10.1093/ijnp/pyw108es_CL


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Atribución-NoComercial-SinDerivadas 3.0 Chile
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