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Psychostimulants and neuroinflammation: finding critical players in the crostalk between glial cells and neurons

dc.contributor.authorBravo, Joana
dc.contributor.authorAndrade, Elva Bonifácio
dc.contributor.authorVieira, Renato
dc.contributor.authorLorga, Inês
dc.contributor.authorAzevedo, M.
dc.contributor.authorRodrigues, J.
dc.contributor.authorMagalhães, Ana
dc.contributor.authorRelvas, João B.
dc.contributor.authorSummavielle, Teresa
dc.contributor.authorSummavielle, Teresa
dc.contributor.authorBonifácio Andrade, Elva
dc.contributor.authorBravo, Joana
dc.date.accessioned2026-01-22T09:17:12Z
dc.date.available2026-01-22T09:17:12Z
dc.date.issued2023-07
dc.description.abstractExposure to psychostimulants has been classically associated with damage to neuronal terminals. However, it is now accepted that interaction between neuronal and glial cells also contributes to the addictive behavior. We have recently shown that acute methamphetamine (Meth), a powerful psychostimulant, causes microgliosis and increases microglia activation through astrocytic-TNF release. We are now interested in clarifying the progression of neuroinflammation under chronic drug exposure and how different brain and immune cells contribute to this inflammatory process.To explore this, firstly, we performed a proteomic analysis, in different phases of the addictive process, in mice exposed to an escalating dosing of Meth for ten days (Meth10d). To validate the conditioning power of our model,mice were tested in a condition place preference (CPP) at 10d of Meth, and 2 or 10 days of withdrawal (WD). At all these time points, mice were seen to be strongly conditioned by Meth. Next, we conducted a proteomic analysis to compare the different time points (using the hippocampus, where we previously found robust microgliosis underMeth). We found a proteome profile that varied substantially with exposure (Meth10d) and after a short- (WD2d)and long-term withdrawal (WD10d) periods. Interestingly, the most altered pathways were neuro transmitter-related. However, we also identified significant differences in Wnt signaling, which was previously linked to regulation of microglia reactivity. As such, we evaluated the microglia profile after chronic Meth exposure and at withdrawal. In the hippocampus, the number of microglia cells was significantly increased at Meth10d and remained also increased at WD2d. Microglia presented a more ameboid-like shape at Meth10d, but its ramified morphology was recovered atWD2d. Importantly, our proteomic data also revealed that during Meth withdrawal, several microglial receptors were down regulated, suggesting that microglia was in a “primed” state. In addition, as the crosstalk between neurons and microglia seems to be relevant for the behavioral expression of Meth, we are dissecting the modulation of microglia by neurons under Meth exposure, to evaluate neuroimmune regulatory ligand-receptor pairs that seem to impact onthe neuron-microglia interaction. Of note, some these ligand-receptor pairs seem to be down regulated by chronic Meth and during abstinence, which may be associated with reduced neuronal ability to down regulate microglia reactivity, and lead to increased neuronal damage.We fore see that these receptors may prove to be interesting therapeutic targets for the treatment of addiction, and therefore we will manipulate them to confirm their value in reducing relapse rates and improve addiction treatments.eng
dc.identifier.citationBravo, J., Andrade, E. B., Vieira, R., Lorga, I., Azevedo, M., Rodrigues, J., Magalhães, A., Relvas, J. B., & Summavielle, T. (2023). Psychostimulants and neuroinflammation: Finding critical players in the crostalk between glial cells and neurons. XVI European Meeting on Glial Cells in Health and Disease 2023 - Abstract booklet, Glia 71, E993–E994. https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24419
dc.identifier.eissn1098-1136
dc.identifier.issn0894-1491
dc.identifier.urihttp://hdl.handle.net/10400.22/31594
dc.language.isoeng
dc.peerreviewedyes
dc.publisherWiley
dc.relationPTDC/SAU-TOX/0067/2021
dc.relation.hasversionhttps://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24419
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectMeth
dc.subjectcondition place preference (CPP)
dc.subjectwithdrawal (WD)
dc.titlePsychostimulants and neuroinflammation: finding critical players in the crostalk between glial cells and neuronseng
dc.typeconference poster
dspace.entity.typePublication
oaire.citation.conferenceDate2023-07
oaire.citation.conferencePlaceBerlin
oaire.citation.endPageE994
oaire.citation.startPageE993
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.familyNameBonifácio Andrade
person.familyNameBravo
person.givenNameTeresa
person.givenNameElva
person.givenNameJoana
person.identifier677706
person.identifier.ciencia-idC41E-0816-5C85
person.identifier.ciencia-id511C-11AA-7980
person.identifier.ciencia-idAA15-F362-062E
person.identifier.orcid0000-0003-2548-6281
person.identifier.orcid0000-0002-1941-580X
person.identifier.orcid0000-0002-8403-7235
person.identifier.ridC-9776-2012
person.identifier.scopus-author-id6603092949
relation.isAuthorOfPublication207ee2de-85a0-4144-9e7e-b376c600e065
relation.isAuthorOfPublicatione3b8883f-57b2-4b83-afa1-88e663ed8d1f
relation.isAuthorOfPublication617f0f54-58dd-45b8-a90f-177187cd197e
relation.isAuthorOfPublication.latestForDiscovery207ee2de-85a0-4144-9e7e-b376c600e065

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