Neuroinflammatory Response to TNFα and IL1β Cytokines Is Accompanied by an Increase in Glycolysis in Human Astrocytes In Vitro

Article Article scientifique Article Neuroinflammatory Response to TNFα and IL1β Cytokines Is Accompanied by an Increase in Glycolysis in Human Astrocytes In Vitro eng 2021-04-14 2021-04-14 author Pamies David author Sartori Chiara author Schvartz Domitille 0000-0003-1133-0462 665782 author Gonzalez Ruiz Victor 0000-0001-7204-2363 831974 author Pellerin Luc author Alonso Patricia Carolina 0000-0001-8503-1719 596377 author Tavel Denise author Maillard Vanille author Boccard Julien 0000-0001-5913-9566 507373 author Rudaz Serge 0000-0002-4180-5417 28978 author Sanchez Jean-Charles 0000-0002-8733-5932 24399 author Zurich Marie-Gabrielle 4065 10.3390/ijms22084065 33920048 1422-0067 PMC8071021 https://www.mdpi.com/1422-0067/22/8/4065 <p>Astrogliosis has been abundantly studied in rodents but relatively poorly in human cells due to limited access to the brain. Astrocytes play important roles in cerebral energy metabolism, and are also key players in neuroinflammation. Astroglial metabolic and inflammatory changes as a function of age have been reported, leading to the hypothesis that mitochondrial metabolism and inflammatory responses are interconnected in supporting a functional switch of astrocytes from neurotrophic to neurotoxic. This study aimed to explore the metabolic changes occurring in astrocytes during their activation. Astrocytes were derived from human ReN cell neural progenitors and characterized. They were activated by exposure to tumor necrosis factor alpha (TNFα) or interleukin 1β (IL1β) for 24 h. Astrocyte reaction and associated energy metabolic changes were assessed by immunostaining, gene expression, proteomics, metabolomics and extracellular flux analyses. ReN-derived astrocytes reactivity was observed by the modifications of genes and proteins linked to inflammation (cytokines, nuclear factor-kappa B (NFκB), signal transducers and activators of transcription (STATs)) and immune pathways (major histocompatibility complex (MHC) class I). Increased NFκB1, NFκB2 and STAT1 expression, together with decreased STAT3 expression, suggest an activation towards the detrimental pathway. Strong modifications of astrocyte cytoskeleton were observed, including a glial fibrillary acidic protein (GFAP) decrease. Astrogliosis was accompanied by changes in energy metabolism characterized by increased glycolysis and lactate release. Increased glycolysis is reported for the first time during human astrocyte activation. Astrocyte activation is strongly tied to energy metabolism, and a possible association between NFκB signaling and/or MHC class I pathway and glycolysis is suggested.</p> Astrocytes Astrogliosis Energy metabolism Neuroenergetic Neuroinflammation Reactive astrocytes Dewey 615 Swiss Centre for Applied Human Toxicology CP3 31 Section des sciences pharmaceutiques 17 false 369 Biomarqueurs 635 881 Sciences analytiques International journal of molecular sciences 22 8 22b8b2fb-79cb-4490-8855-20a81e0b74ed Article (Published version) Public Pamies2021.pdf 5647419 application/pdf CC BY-4.0 openAccess Faculté des sciences / Section des sciences pharmaceutiques

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Neuroinflammatory Response to TNFα and IL1β Cytokines Is Accompanied by an Increase in Glycolysis in Human Astrocytes In Vitro	International journal of molecular sciences			2021	219	131

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