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Astrocyte-derived TNF and glutamate critically modulate microglia activation by methamphetamine

2021-08-16Journal article Open access
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dc.contributor.authorCanedo, Teresa
dc.contributor.authorPortugal, Camila Cabral
dc.contributor.authorSocodato, Renato
dc.contributor.authorAlmeida, Tiago Oliveira
dc.contributor.authorTerceiro, Ana Filipa
dc.contributor.authorBravo, Joana
dc.contributor.authorSilva, Ana Isabel
dc.contributor.authorMagalhães, João Duarte
dc.contributor.authorGuerra-Gomes, Sónia
dc.contributor.authorOliveira, João Filipe
dc.contributor.authorSousa, Nuno
dc.contributor.authorMagalhães, Ana
dc.contributor.authorRelvas, João Bettencourt
dc.contributor.authorSummavielle, Teresa
dc.date.accessioned2024-03-05T13:05:41Z
dc.date.available2024-03-05T13:05:41Z
dc.date.issued2021-08-16
dc.description.abstractMethamphetamine (Meth) is a powerful illicit psychostimulant, widely used for recreational purposes. Besides disrupting the monoaminergic system and promoting oxidative brain damage, Meth also causes neuroinflammation, contributing to synaptic dysfunction and behavioral deficits. Aberrant activation of microglia, the largest myeloid cell population in the brain, is a common feature in neurological disorders triggered by neuroinflammation. In this study, we investigated the mechanisms underlying the aberrant activation of microglia elicited by Meth in the adult mouse brain. We found that binge Meth exposure caused microgliosis and disrupted risk assessment behavior (a feature that usually occurs in individuals who abuse Meth), both of which required astrocyte-to-microglia crosstalk. Mechanistically, Meth triggered a detrimental increase of glutamate exocytosis from astrocytes (in a process dependent on TNF production and calcium mobilization), promoting microglial expansion and reactivity. Ablating TNF production, or suppressing astrocytic calcium mobilization, prevented Meth-elicited microglia reactivity and re-established risk assessment behavior as tested by elevated plus maze (EPM). Overall, our data indicate that glial crosstalk is critical to relay alterations caused by acute Meth exposure.pt_PT
dc.description.sponsorship207/14/Fundação Bial (Bial Foundation) 037/18/Fundação Bial (Bial Foundation)pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCanedo, T., Portugal, C. C., Socodato, R., Almeida, T. O., Terceiro, A. F., Bravo, J., Silva, A. I., Magalhães, J. D., Guerra-Gomes, S., Oliveira, J. F., Sousa, N., Magalhães, A., Relvas, J. B., & Summavielle, T. (2021). Astrocyte-derived TNF and glutamate critically modulate microglia activation by methamphetamine. Neuropsychopharmacology, 46(13), 2358–2370. https://doi.org/10.1038/s41386-021-01139-7pt_PT
dc.identifier.doi10.1038/s41386-021-01139-7pt_PT
dc.identifier.eissn1740-634X
dc.identifier.issn0893-133X
dc.identifier.urihttp://hdl.handle.net/10400.22/25125
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherNaturept_PT
dc.relationSFRH/BD/117148/2016pt_PT
dc.relationSFRH/BD/147981/2019pt_PT
dc.relation2020.07188.BDpt_PT
dc.relationPD/BD/135450/2017pt_PT
dc.relationSFRH/BD/144324/2019pt_PT
dc.relationPTDC/MED-NEU/31417/2017pt_PT
dc.relationUIDB/50026/2020pt_PT
dc.relationIF/00753/2014pt_PT
dc.relationPTDC/SAU-TOX/30647/2017pt_PT
dc.relation.publisherversionhttps://www.nature.com/articles/s41386-021-01139-7pt_PT
dc.subjectMethamphetamine (Meth)pt_PT
dc.subjectPsychostimulantpt_PT
dc.titleAstrocyte-derived TNF and glutamate critically modulate microglia activation by methamphetaminept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage2370pt_PT
oaire.citation.startPage2358pt_PT
oaire.citation.titleNeuropsychopharmacologypt_PT
oaire.citation.volume46pt_PT
person.familyNameBravo
person.familyNameSummavielle
person.givenNameJoana
person.givenNameTeresa
person.identifier677706
person.identifier.ciencia-idAA15-F362-062E
person.identifier.ciencia-idC41E-0816-5C85
person.identifier.orcid0000-0002-8403-7235
person.identifier.orcid0000-0003-2548-6281
person.identifier.ridC-9776-2012
person.identifier.scopus-author-id6603092949
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication617f0f54-58dd-45b8-a90f-177187cd197e
relation.isAuthorOfPublication207ee2de-85a0-4144-9e7e-b376c600e065
relation.isAuthorOfPublication.latestForDiscovery207ee2de-85a0-4144-9e7e-b376c600e065

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