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Methamphetamine activates rac1 in striatal microglia

dc.contributor.authorTerceiro, Ana Filipa
dc.contributor.authorCanedo, Teresa
dc.contributor.authorSilva, Ana Isabel
dc.contributor.authorMagalhães, Ana
dc.contributor.authorRelvas, João
dc.contributor.authorSummavielle, Teresa
dc.contributor.authorSummavielle, Teresa
dc.date.accessioned2026-01-22T09:17:27Z
dc.date.available2026-01-22T09:17:27Z
dc.date.issued2023-07-01
dc.description.abstractMethamphetamine (Meth), a powerful psychostimulant, induces profound synaptic and morphological alterations alongside with detrimental neuroinflammatory responses, in the brain reward system. Yet, the mechanisms regulating these processes in microglial cells are not clear. We have previously shown that exposing WT mice to Meth (4x5mg/kg, 2h intervals) induces microgliosis concomitant with decreased microglia cell volume and ramification. Furthermore, psychostimulants are known to induce structural plasticity mechanisms in neurons, and Rho GTPases, important regulators of the actin cytoskeleton, are involved in these responses. Here, we evaluate if Rho GTPases, specifically rhoA, rac1 and cdc42, are critical in the response to Meth in microglia. Exposing WT mice to the samepattern of Meth administration, we found an increase in the activation of rac1 in the striatum, 15 min following the last administration of Meth. To further explore these results, we then used a conditional mice model for ablation of rac1 in adult microglia (Rac1fl/fl:Cx3cr1CreER+) and exposed these mutants to the same pattern of Meth administration. We found that rac1 ablation is sufficient to prevent Meth-induced morphological alterations in the striatum. Currently, we are assessing whether ablation of rac1 is also sufficient to prevent the neuroinflammatory response induced by Meth. Overall, we identified rac1 as a novel target of Meth in microglial cells. With these results, we expect to clarifyif targeting Rho GTPases may contribute to improving the treatment of addictive disorders.eng
dc.identifier.citationTerceiro, A. F., Canedo, T., Silva, A. I., Magalhães, A., Relvas, J., & Summavielle, T. (2023). Methamphetamine activates rac1 in striatal microglia. XVI European Meeting on Glial Cells in Health and Disease 2023 - Abstract booklet, Glia 71, E252. https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24419
dc.identifier.eissn1098-1136
dc.identifier.issn0894-1491
dc.identifier.urihttp://hdl.handle.net/10400.22/31596
dc.language.isoeng
dc.peerreviewedyes
dc.publisherWiley
dc.relation.hasversionhttps://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24419
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectMeth
dc.subjectRho GTPases
dc.titleMethamphetamine activates rac1 in striatal microgliaeng
dc.typeconference poster
dspace.entity.typePublication
oaire.citation.conferenceDate2023-07
oaire.citation.conferencePlaceBerlin
oaire.citation.startPageE252
oaire.citation.titleXVI European Meeting on Glial Cells in Health and Disease 2023 - Abstract booklet - Glia
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameSummavielle
person.givenNameTeresa
person.identifier677706
person.identifier.ciencia-idC41E-0816-5C85
person.identifier.orcid0000-0003-2548-6281
person.identifier.ridC-9776-2012
person.identifier.scopus-author-id6603092949
relation.isAuthorOfPublication207ee2de-85a0-4144-9e7e-b376c600e065
relation.isAuthorOfPublication.latestForDiscovery207ee2de-85a0-4144-9e7e-b376c600e065

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