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dc.contributor.authorVizuete, Adriana Fernanda Kuckartzpt_BR
dc.contributor.authorFróes, Fernanda Carolina Telles da Silvapt_BR
dc.contributor.authorSeady, Marina Pedrapt_BR
dc.contributor.authorBoeckel, Caroline Zanotto dept_BR
dc.contributor.authorBobermin, Larissa Danielept_BR
dc.contributor.authorRoginski, Ana Cristinapt_BR
dc.contributor.authorWajner, Moacirpt_BR
dc.contributor.authorQuincozes-Santos, Andrépt_BR
dc.contributor.authorGoncalves, Carlos Alberto Saraivapt_BR
dc.date.accessioned2023-02-07T05:02:48Zpt_BR
dc.date.issued2022pt_BR
dc.identifier.issn1742-2094pt_BR
dc.identifier.urihttp://hdl.handle.net/10183/254322pt_BR
dc.description.abstractNeuroinflammation is a common feature during the development of neurological disorders and neurodegenerative diseases, where glial cells, such as microglia and astrocytes, play key roles in the activation and maintenance of inflammatory responses in the central nervous system. Neuroinflammation is now known to involve a neurometabolic shift, in addition to an increase in energy consumption. We used two approaches (in vivo and ex vivo) to evaluate the effects of lipopolysaccharide (LPS)-induced neuroinflammation on neurometabolic reprogramming, and on the modulation of the glycolytic pathway during the neuroinflammatory response. For this, we investigated inflammatory cytokines and receptors in the rat hippocampus, as well as markers of glial reactivity. Mitochondrial respirometry and the glycolytic pathway were evaluated by multiple parameters, including enzymatic activity, gene expression and regulation by protein kinases. Metabolic (e.g., metformin, 3PO, oxamic acid, fluorocitrate) and inflammatory (e.g., minocycline, MCC950, arundic acid) inhibitors were used in ex vivo hippocampal slices. The induction of early inflammatory changes by LPS (both in vivo and ex vivo) enhanced glycolytic parameters, such as glucose uptake, PFK1 activity and lactate release. This increased glucose consumption was independent of the energy expenditure for glutamate uptake, which was in fact diverted for the maintenance of the immune response. Accordingly, inhibitors of the glycolytic pathway and Krebs cycle reverted neuroinflammation (reducing IL-1β and S100B) and the changes in glycolytic parameters induced by LPS in acute hippocampal slices. Moreover, the inhibition of S100B, a protein predominantly synthesized and secreted by astrocytes, inhibition of microglia activation and abrogation of NLRP3 inflammasome assembly confirmed the role of neuroinflammation in the upregulation of glycolysis in the hippocampus. Our data indicate a neurometabolic glycolytic shift, induced by inflammatory activation, as well as a central and integrative role of astrocytes, and suggest that interference in the control of neurometabolism may be a promising strategy for downregulating neuroinflammation and consequently for diminishing negative neurological outcomes.en
dc.format.mimetypeapplication/pdfpt_BR
dc.language.isoengpt_BR
dc.relation.ispartofJournal of neuroinflammation. London. Vol. 19 (Oct. 2022), 255, 23 p.pt_BR
dc.rightsOpen Accessen
dc.subjectNeuroinflammationen
dc.subjectHipocampopt_BR
dc.subjectDoenças neuroinflamatóriaspt_BR
dc.subjectGlycolysisen
dc.subjectGlucose uptakeen
dc.subjectGlicólisept_BR
dc.subjectPFK1en
dc.subjectGlucosept_BR
dc.subjectLipopolissacarídeospt_BR
dc.subjectS100Ben
dc.subjectMetabolismopt_BR
dc.subjectIL-1βen
dc.subjectDoenças do sistema nervosopt_BR
dc.titleEarly effects of LPS-induced neuroinflammation on the rat hippocampal glycolytic pathwaypt_BR
dc.typeArtigo de periódicopt_BR
dc.identifier.nrb001158312pt_BR
dc.type.originEstrangeiropt_BR


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