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Open AccessArticle

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

1
Department of Biomedical Sciences, University of Lausanne, CH-1005 Lausanne, Switzerland
2
Swiss Centre for Applied Human Toxicology (SCAHT), 4055 Basel, Switzerland
3
Translational Biomarker Group, Department of Internal Medicine Specialties, University of Geneva, CH-1211 Genève, Switzerland
4
Analytical Sciences, Institute of Pharmaceutical Sciences of Western Switzerland and School of Pharmaceutical Sciences, University of Geneva, CH-1211 Genève, Switzerland
5
INSERM U1082, Faculté de Médecine et de Pharmacie, Université de Poitiers, F-86021 Poitiers, France
*
Author to whom correspondence should be addressed.
Academic Editor: Antonella Scorziello
Int. J. Mol. Sci. 2021, 22(8), 4065; https://doi.org/10.3390/ijms22084065
Received: 17 March 2021 / Revised: 2 April 2021 / Accepted: 6 April 2021 / Published: 14 April 2021
(This article belongs to the Section Molecular Neurobiology)
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. View Full-Text
Keywords: astrocytes; astrogliosis; reactive astrocytes; neuroinflammation; energy metabolism; neuroenergetic astrocytes; astrogliosis; reactive astrocytes; neuroinflammation; energy metabolism; neuroenergetic
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MDPI and ACS Style

Pamies, D.; Sartori, C.; Schvartz, D.; González-Ruiz, V.; Pellerin, L.; Nunes, C.; Tavel, D.; Maillard, V.; Boccard, J.; Rudaz, S.; Sanchez, J.-C.; Zurich, M.-G. Neuroinflammatory Response to TNFα and IL1β Cytokines Is Accompanied by an Increase in Glycolysis in Human Astrocytes In Vitro. Int. J. Mol. Sci. 2021, 22, 4065. https://doi.org/10.3390/ijms22084065

AMA Style

Pamies D, Sartori C, Schvartz D, González-Ruiz V, Pellerin L, Nunes C, Tavel D, Maillard V, Boccard J, Rudaz S, Sanchez J-C, Zurich M-G. 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; 22(8):4065. https://doi.org/10.3390/ijms22084065

Chicago/Turabian Style

Pamies, David; Sartori, Chiara; Schvartz, Domitille; González-Ruiz, Víctor; Pellerin, Luc; Nunes, Carolina; Tavel, Denise; Maillard, Vanille; Boccard, Julien; Rudaz, Serge; Sanchez, Jean-Charles; Zurich, Marie-Gabrielle. 2021. "Neuroinflammatory Response to TNFα and IL1β Cytokines Is Accompanied by an Increase in Glycolysis in Human Astrocytes In Vitro" Int. J. Mol. Sci. 22, no. 8: 4065. https://doi.org/10.3390/ijms22084065

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