Co-treatment with verapamil and curcumin attenuates the behavioral alterations observed in Williams-Beuren syndrome mice by regulation of MAPK pathway and microglia overexpression

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• dc.contributor.author Ortiz Romero, Paula, 1994-
• dc.contributor.author González-Simón, Alejandro
• dc.contributor.author Egea, Gustavo
• dc.contributor.author Pérez Jurado, Luis Alberto
• dc.contributor.author Campuzano Uceda, María Victoria
• dc.date.accessioned 2021-10-14T06:21:28Z
• dc.date.available 2021-10-14T06:21:28Z
• dc.date.issued 2021
• dc.description.abstract Williams-Beuren syndrome (WBS) is a rare neurodevelopmental disorder characterized by a distinctive cognitive phenotype for which there are currently no effective treatments. We investigated the progression of behavioral deficits present in WBS complete deletion (CD) mice, after chronic treatment with curcumin, verapamil, and a combination of both. These compounds have been proven to have beneficial effects over different cognitive aspects of various murine models and, thus, may have neuroprotective effects in WBS. Treatment was administered orally dissolved in drinking water. A set of behavioral tests demonstrated the efficiency of combinatorial treatment. Some histological and molecular analyses were performed to analyze the effects of treatment and its underlying mechanism. CD mice showed an increased density of activated microglia in the motor cortex and CA1 hippocampal region, which was prevented by co-treatment. Behavioral improvement correlated with the molecular recovery of several affected pathways regarding MAPK signaling, in tight relation to the control of synaptic transmission, and inflammation. Therefore, the results show that co-treatment prevented behavioral deficits by recovering altered gene expression in the cortex of CD mice and reducing activated microglia. These findings unravel the mechanisms underlying the beneficial effects of this novel treatment on behavioral deficits observed in CD mice and suggest that the combination of curcumin and verapamil could be a potential candidate to treat the cognitive impairments in WBS patients.
• dc.description.sponsorship This work was supported by Ministerio de Ciencia e Innovación (SAF 2017-83039-R to GE and SAF 2016-78508-R (AEI/MINEICO/FEDER, UE) to VC) from the association “Autour des Williams” to VC and Generalitat de Catalunya (2017-SGR1794) to VC.
• dc.format.mimetype application/pdf
• dc.identifier.citation Ortiz-Romero P, González-Simón A, Egea G, Pérez-Jurado LA, Campuzano V. Co-treatment with verapamil and curcumin attenuates the behavioral alterations observed in Williams-Beuren syndrome mice by regulation of MAPK pathway and microglia overexpression. Front Pharmacol. 2021 Aug 3;12:670785. DOI: 10.3389/fphar.2021.670785
• dc.identifier.doi http://dx.doi.org/10.3389/fphar.2021.670785
• dc.identifier.issn 1663-9812
• dc.identifier.uri http://hdl.handle.net/10230/48645
• dc.language.iso eng
• dc.publisher Frontiers
• dc.relation.ispartof Front Pharmacol. 2021 Aug 3;12:670785
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/SAF2017-83039-R
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-78508-R
• dc.rights © 2021 Ortiz-Romero, González-Simón, Egea, Pérez-Jurado and Campuzano. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Williams–Beuren syndrome
• dc.subject.keyword Activated glia
• dc.subject.keyword Behavior
• dc.subject.keyword Curcumin
• dc.subject.keyword Mice
• dc.subject.keyword Verapamil
• dc.title Co-treatment with verapamil and curcumin attenuates the behavioral alterations observed in Williams-Beuren syndrome mice by regulation of MAPK pathway and microglia overexpression
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion