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

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dc.contributor.authorGarcía-Rojo, G.
dc.contributor.authorFresno, C.
dc.contributor.authorVilches, N.
dc.contributor.authorDíaz-Véliz, G.
dc.contributor.authorMora, S.
dc.contributor.authorAguayo, F.
dc.contributor.authorPacheco, A.
dc.contributor.authorParra-Fiedler, N.
dc.contributor.authorParra, C.S.
dc.contributor.authorRojas, P.S.
dc.contributor.authorTejos, M.
dc.contributor.authorAliaga, E.
dc.contributor.authorFiedler, J.L.
dc.date.accessioned2017-11-24T14:21:53Z
dc.date.available2017-11-24T14:21:53Z
dc.date.issued2017-04
dc.descriptionIndexación: Web of Science; Scopus.es_CL
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. Conclusion: Our findings suggest that Fasudil may prevent the development of abnormal behavior and spine loss induced by chronic stress by blocking Rho kinase activity.es_CL
dc.description.urihttps://academic.oup.com/ijnp/article/20/4/336/2632175
dc.identifier.citationInternational Journal of Neuropsychopharmacology. Volume 20, Issue 4, 1 April 2017, Pages 336-345es_CL
dc.identifier.issn1461-1457
dc.identifier.otherDOI: 10.1093/ijnp/pyw108
dc.identifier.urihttp://repositorio.unab.cl/xmlui/handle/ria/4722
dc.language.isoenes_CL
dc.publisherOxford University Presses_CL
dc.rights.licenseAttribution-NonCommercial 4.0 International (CC BY-NC 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.subjectAntidepressantes_CL
dc.subjectBehavior Dendritic spineses_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.typeArtículoes_CL
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