Early effects of LPS-induced neuroinflammation on the rat hippocampal glycolytic pathway
dc.contributor.author | Vizuete, Adriana Fernanda Kuckartz | pt_BR |
dc.contributor.author | Fróes, Fernanda Carolina Telles da Silva | pt_BR |
dc.contributor.author | Seady, Marina Pedra | pt_BR |
dc.contributor.author | Boeckel, Caroline Zanotto de | pt_BR |
dc.contributor.author | Bobermin, Larissa Daniele | pt_BR |
dc.contributor.author | Roginski, Ana Cristina | pt_BR |
dc.contributor.author | Wajner, Moacir | pt_BR |
dc.contributor.author | Quincozes-Santos, André | pt_BR |
dc.contributor.author | Goncalves, Carlos Alberto Saraiva | pt_BR |
dc.date.accessioned | 2023-02-07T05:02:48Z | pt_BR |
dc.date.issued | 2022 | pt_BR |
dc.identifier.issn | 1742-2094 | pt_BR |
dc.identifier.uri | http://hdl.handle.net/10183/254322 | pt_BR |
dc.description.abstract | Neuroinflammation 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.mimetype | application/pdf | pt_BR |
dc.language.iso | eng | pt_BR |
dc.relation.ispartof | Journal of neuroinflammation. London. Vol. 19 (Oct. 2022), 255, 23 p. | pt_BR |
dc.rights | Open Access | en |
dc.subject | Neuroinflammation | en |
dc.subject | Hipocampo | pt_BR |
dc.subject | Doenças neuroinflamatórias | pt_BR |
dc.subject | Glycolysis | en |
dc.subject | Glucose uptake | en |
dc.subject | Glicólise | pt_BR |
dc.subject | PFK1 | en |
dc.subject | Glucose | pt_BR |
dc.subject | Lipopolissacarídeos | pt_BR |
dc.subject | S100B | en |
dc.subject | Metabolismo | pt_BR |
dc.subject | IL-1β | en |
dc.subject | Doenças do sistema nervoso | pt_BR |
dc.title | Early effects of LPS-induced neuroinflammation on the rat hippocampal glycolytic pathway | pt_BR |
dc.type | Artigo de periódico | pt_BR |
dc.identifier.nrb | 001158312 | pt_BR |
dc.type.origin | Estrangeiro | pt_BR |
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