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Intersectin1/cdc42 signaling regulates methamphetamine-induced neuronal remodeling in the hippocampus

2025-08-25Artigo de investigação Acesso aberto
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dc.contributor.authorTerceiro, Ana Filipa
dc.contributor.authorLobo, Andrea
dc.contributor.authorSocodato, Renato
dc.contributor.authorCanedo, Teresa
dc.contributor.authorSilva, Ana Isabel
dc.contributor.authorCavadas, Bruno
dc.contributor.authorCarvalhais, Lia G.
dc.contributor.authorAroso, Miguel
dc.contributor.authorMorello, Gabriela M.
dc.contributor.authorAguiar, Paulo
dc.contributor.authorMagalhães, Ana
dc.contributor.authorCarvalho, Ana Luísa
dc.contributor.authorRelvas, João B.
dc.contributor.authorFonseca, Rosalina
dc.contributor.authorSummavielle, Teresa
dc.contributor.authorSummavielle, Teresa
dc.date.accessioned2026-06-29T09:26:54Z
dc.date.available2026-06-29T09:26:54Z
dc.date.issued2025-08-25
dc.description.abstractThe development and maintenance of drug addiction triggered by psychoactive substances, such as methamphetamine (Meth), is strongly influenced by synaptic and morphological adaptations in the brain. The hippocampus has a key role in the formation of maladaptive drug-context associations and relapse. However, the mechanisms regulating this complex process are not completely understood. Recent studies highlight that the actin cytoskeleton and its regulatory proteins play a fundamental role in morphological and behavioral plasticity associated with drug use. Here, we show that a binge pattern of Meth administration is sufficient to increase hippocampal neurite outgrowth and dendritic spine density leading to augmented basal synaptic transmission and impaired long-term potentiation (LTP) response. To study the molecular pathways affected by Meth, we used embryonic primary neuron cultures from the hippocampus and performed RNA Sequencing from isolated soma or neurites compartments, FRET microscopy, biochemical analyses, and morphometric measurements of dendrites to demonstrate that intersectin (Itsn)1/cdc42 signaling is an important mediator of Meth-induced morphological adaptations, specifically in the synaptic compartment. Furthermore, AAV-mediated depletion of neuronal cdc42 in the hippocampus prevented Meth-induced changes in cytoarchitecture and their consequent impact on neuronal functionality. Our results highlight relevant compartment-associated changes in the activity of Itsn1/cdc42 pathway that critically regulate Meth-induced neuronal remodeling and plasticity.eng
dc.description.sponsorshipNORTE2030-FEDER-01711200
dc.identifier.citationTerceiro, A. F., Lobo, A., Socodato, R., Canedo, T., Silva, A. I., Cavadas, B., Carvalhais, L. G., Aroso, M., Morello, G. M., Aguiar, P., Magalhães, A., Carvalho, A. L., Relvas, J. B., Fonseca, R., & Summavielle, T. (2025). Intersectin1/cdc42 signaling regulates methamphetamine-induced neuronal remodeling in the hippocampus. Cellular and Molecular Life Sciences, 82(1), 387. https://doi.org/10.1007/s00018-025-05890-8
dc.identifier.doi10.1007/s00018-025-05890-8
dc.identifier.eissn1420-9071
dc.identifier.issn1420-682X
dc.identifier.urihttp://hdl.handle.net/10400.22/32526
dc.language.isoeng
dc.peerreviewedyes
dc.publisherSpringer Nature
dc.relationPTDC/ SAU-TOX/0067/2021; SFRH/BD/144324/2019, 2020.07188.BD; 023.06380. CEECIND. TS, BC and RF are funded by FCT through 2022.03699. CEECIND CEECINST/00123/2021 and CEECINST.2802.2022
dc.relation.hasversionhttps://link.springer.com/article/10.1007/s00018-025-05890-8
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectrhoGTPases
dc.subjectAddiction
dc.subjectPsychostimulants
dc.subjectNeuronal-morphology
dc.subjectSynaptic plasticity
dc.titleIntersectin1/cdc42 signaling regulates methamphetamine-induced neuronal remodeling in the hippocampuseng
dc.typeresearch article
dspace.entity.typePublication
oaire.citation.titleCellular and Molecular Life Sciences
oaire.citation.volume82
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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