Publication
IL-10 and Cdc42 modulate astrocyte-mediated microglia activation in methamphetamine-induced neuroinflammation
| dc.contributor.author | Silva, Ana Isabel | |
| dc.contributor.author | Socodato, Renato | |
| dc.contributor.author | Pinto, Carolina | |
| dc.contributor.author | Terceiro, Ana Filipa | |
| dc.contributor.author | Canedo, Teresa | |
| dc.contributor.author | Relvas, João Bettencourt | |
| dc.contributor.author | Saraiva, Margarida | |
| dc.contributor.author | Summavielle, Teresa | |
| dc.date.accessioned | 2024-10-09T10:02:00Z | |
| dc.date.embargo | 2025-05 | |
| dc.date.issued | 2024-05-23 | |
| dc.description.abstract | Methamphetamine (Meth) use is known to induce complex neuroinflammatory responses, particularly involving astrocytes and microglia. Building upon our previous research, which demonstrated that Meth stimulates astrocytes to release tumor necrosis factor (TNF) and glutamate, leading to microglial activation, this study investigates the role of the anti-inflammatory cytokine interleukin-10 (IL-10) in this process. Our findings reveal that the presence of recombinant IL-10 (rIL-10) counteracts Meth-induced excessive glutamate release in astrocyte cultures, which significantly reduces microglial activation. This reduction is associated with the modulation of astrocytic intracellular calcium (Ca2+) dynamics, particularly by restricting the release of Ca2+ from the endoplasmic reticulum to the cytoplasm. Furthermore, we identify the small Rho GTPase Cdc42 as a crucial intermediary in the astrocyte-to-microglia communication pathway under Meth exposure. By employing a transgenic mouse model that overexpresses IL-10 (pMT-10), we also demonstrate in vivo that IL-10 prevents Meth-induced neuroinflammation. These findings not only enhance our understanding of Meth-related neuroinflammatory mechanisms, but also suggest IL-10 and Cdc42 as putative therapeutic targets for treating Meth-induced neuroinflammation. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | Silva, A. I., Socodato, R., Pinto, C., Terceiro, A. F., Canedo, T., Relvas, J. B., Saraiva, M., & Summavielle, T. (2024). IL-10 and Cdc42 modulate astrocyte-mediated microglia activation in methamphetamine-induced neuroinflammation. Glia, 72(8), 1501–1517. https://doi.org/10.1002/glia.24542 | pt_PT |
| dc.identifier.doi | 10.1002/glia.24542 | pt_PT |
| dc.identifier.eissn | 1098-1136 | |
| dc.identifier.issn | 0894-1491 | |
| dc.identifier.uri | http://hdl.handle.net/10400.22/26222 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | Wiley | pt_PT |
| dc.relation | This work was funded by National Funds through FCT—Fundação para a Ciência e a Tecnologia, I.P., under the project PTDC/SAU-TOX/0067/2021 in Summavielle's lab, this project has also supported the work of TC. AIS and AFT were supported by FCT (SFRH/BD/144324/2019, 2020.07188.BD). RS holds employment contracts financed by national funds through FCT–in the context of the program-contract described in paragraphs 4, 5, and 6 of art. 23 of Law no. 57/ 2016, of August 29, as amended by Law no. 57/2017 of July 2019. TS and MS are funded by FCT through 2022.03699.CEECIND and CEECIND/00241/2017, respectively. We acknowledge the support of the following i3S Scientific Platforms: BioSciences Screening, member of the PT-OPENSCREEN (NORTE-01-0145-FEDER-085468) and advanced light microscopy (ALM), a member of the national infrastructure PPBI-Portuguese Platform of BioImaging (supported by POCI-01-0145-FEDER-022122), and animal facility, and we thank André Maia, António Pombinho, Maria Azevedo, and Sofia Lamas from these facilities for their technical support. | pt_PT |
| dc.relation.publisherversion | https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24542 | pt_PT |
| dc.subject | Cytokines | pt_PT |
| dc.subject | Glia | pt_PT |
| dc.subject | Interleukin-10 | pt_PT |
| dc.subject | Psychostimulants | pt_PT |
| dc.subject | rho GTPase | pt_PT |
| dc.title | IL-10 and Cdc42 modulate astrocyte-mediated microglia activation in methamphetamine-induced neuroinflammation | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 1517 | pt_PT |
| oaire.citation.startPage | 1501 | pt_PT |
| oaire.citation.title | GLIA | pt_PT |
| oaire.citation.volume | 72 (8) | pt_PT |
| person.familyName | Summavielle | |
| person.givenName | Teresa | |
| person.identifier | 677706 | |
| person.identifier.ciencia-id | C41E-0816-5C85 | |
| person.identifier.orcid | 0000-0003-2548-6281 | |
| person.identifier.rid | C-9776-2012 | |
| person.identifier.scopus-author-id | 6603092949 | |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | article | pt_PT |
| relation.isAuthorOfPublication | 207ee2de-85a0-4144-9e7e-b376c600e065 | |
| relation.isAuthorOfPublication.latestForDiscovery | 207ee2de-85a0-4144-9e7e-b376c600e065 |