Nerve Growth Factor modulates LPS - induced microglial glycolysis and inflammatory responses

Fodelianaki, Georgia; Lansing, Felix; Bhattarai, Prabesh; Troullinaki, Maria; Zeballos, Maria Alejandra; Charalampopoulos, Ioannis; Gravanis, Achille; Mirtschink, Peter; Chavakis, Triantafyllos; Alexaki, Vasileia Ismini

doi:10.1016/j.yexcr.2019.02.023

Cited by 51 publications

(43 citation statements)

References 34 publications

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“…In line with these results, treatment of LPS/Aβ-stimulated primary microglial cells with anti-TLR2 antibody inhibited the expression of glycolytic enzyme (PFKFB3), as well as reduced the proinflammatory cytokine release and enhanced the phagocytic ability (Rubio-Araiz et al, 2018). Neurotrophins and nerve growth factor (NGF) inhibited LPS-stimulated primary microglial responses by downregulating the glycolytic enzymes Pfkβ3 and Ldhα (Fodelianaki et al, 2019).…”

Section: Modulation Of Glial Metabolism As a Therapeutic Strategysupporting

confidence: 59%

Metabolic Regulation of Glial Phenotypes: Implications in Neuron–Glia Interactions and Neurological Disorders

Afridi

Kim

Rahman

et al. 2020

Front. Cell. Neurosci.

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Glial cells are multifunctional, non-neuronal components of the central nervous system with diverse phenotypes that have gained much attention for their close involvement in neuroinflammation and neurodegenerative diseases. Glial phenotypes are primarily characterized by their structural and functional changes in response to various stimuli, which can be either neuroprotective or neurotoxic. The reliance of neurons on glial cells is essential to fulfill the energy demands of the brain for its proper functioning. Moreover, the glial cells perform distinct functions to regulate their own metabolic activities, as well as work in close conjunction with neurons through various secreted signaling or guidance molecules, thereby constituting a complex network of neuron-glial interactions in health and disease. The emerging evidence suggests that, in disease conditions, the metabolic alterations in the glial cells can induce structural and functional changes together with neuronal dysfunction indicating the importance of neuron-glia interactions in the pathophysiology of neurological disorders. This review covers the recent developments that implicate the regulation of glial phenotypic changes and its consequences on neuron-glia interactions in neurological disorders. Finally, we discuss the possibilities and challenges of targeting glial metabolism as a strategy to treat neurological disorders.

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Section: Modulation Of Glial Metabolism As a Therapeutic Strategysupporting

confidence: 59%

Metabolic Regulation of Glial Phenotypes: Implications in Neuron–Glia Interactions and Neurological Disorders

Afridi

Kim

Rahman

et al. 2020

Front. Cell. Neurosci.

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“…Although it has garnered increasing attention, the definitive link between in situ microglial metabolism, their immune functions, and impacts on synaptic plasticity remain unclear (Baik et al, 2019;Fodelianaki et al, 2019;Lynch, 2020;Nair et al, 2019;Wang et al, 2019). The study of immunometabolism in microglia has proven challenging, as these cells are highly sensitive to changes in their environment.…”

Section: Introductionmentioning

confidence: 99%

Neuroinflammatory inhibition of synaptic long‐term potentiation requires immunometabolic reprogramming of microglia

York

Zhang

Choi

et al. 2020

Glia

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Immunometabolism refers to the rearrangement of metabolic pathways in response to immune stimulation, and the ability of these metabolic pathways themselves to control immune functions. Many aspects of immunometabolism have been revealed through studies of peripheral immune cells. However, immunometabolic reprogramming of microglia, the resident immune cell of the central nervous system, and the consequential outcome on neuronal activity have remained difficult to unravel. Microglia are highly sensitive to subtle changes in their environment, limiting the techniques available to study their metabolic and inflammatory profiles. Here, using fluorescence lifetime imaging of endogenous NAD(P)H, we measure the metabolic activity of individual microglia within acute hippocampal slices. We observed an LPS‐induced increase in aerobic glycolysis, which was blocked by the addition of 5 mM 2‐deoxyglucose (2DG). This LPS‐induced glycolysis in microglia was necessary for the stabilization of hypoxia inducible factor‐1α (HIF‐1α) and production of the proinflammatory cytokine, interleukin‐1β (IL‐1β). Upon release, IL‐1β acted via the neuronal interleukin‐1 receptor to inhibit the formation of synaptic long‐term potentiation (LTP) following high frequency stimulation. Remarkably, the addition of 2DG to blunt the microglial glycolytic increase also inhibited HIF‐1α accumulation and IL‐1β production, and therefore rescued LTP in LPS‐stimulated slices. Overall, these data reveal the importance of metabolic reprogramming in regulating microglial immune functions, with appreciable outcomes on cytokine release and neuronal activity.

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“…In the present study, the trends of MGO and D -lactate levels correlated positively with renal damage and were reversed with SSC treatment. Glycolysis is enhanced during renal damage, since inflammation and repair require a high consumption of energy [ 59 ]. During glycolysis, glucose is first converted into fructose 1,6-bisphosphate via phosphorylation [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Utilizing methylglyoxal and D-lactate in urine to evaluate saikosaponin C treatment in mice with accelerated nephrotoxic serum nephritis

et al. 2020

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The relationship between methylglyoxal (MGO) and D -lactate during saikosaponin C (SSC) treatment of mice with accelerated nephrotoxic serum (NTS) nephritis was investigated. NTS nephritis was induced by administration of anti-basement membrane antibodies to C57BL/6 mice and three dosages of SSC were administered for 14 days. Proteinuria, blood urea nitrogen, serum creatinine, renal histology, urinary MGO and d -lactate changes were examined. Compared to the NTS control group, the middle dosage (10 mg/kg/day) of SSC significantly alleviated the development of nephritis based on urine protein measurements (34.40 ± 6.85 vs. 17.33 ± 4.79 mg/day, p <0.05). Pathological observation of the glomerular basement membrane (GBM) revealed monocyte infiltration, hypertrophy, and crescents were alleviated, and injury scoring also showed improved efficacy for the middle dose of SSC during nephritis (7.92 ± 1.37 vs. 3.50 ± 1.14, p <0.05). Moreover, the significant decreases in urinary levels of MGO (24.71 ± 3.46 vs. 16.72 ± 2.36 μg/mg, p <0.05) and D -lactate (0.31 ± 0.04 vs. 0.23 ± 0.02 μmol/mg, p <0.05) were consistent with the biochemical and pathological examinations. This study demonstrates that MGO and D -lactate may reflect the extent of damage and the efficacy of SSC in NTS nephritis; further studies are required to enable clinical application.

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Nerve Growth Factor modulates LPS - induced microglial glycolysis and inflammatory responses

Cited by 51 publications

References 34 publications

Metabolic Regulation of Glial Phenotypes: Implications in Neuron–Glia Interactions and Neurological Disorders

Metabolic Regulation of Glial Phenotypes: Implications in Neuron–Glia Interactions and Neurological Disorders

Neuroinflammatory inhibition of synaptic long‐term potentiation requires immunometabolic reprogramming of microglia

Utilizing methylglyoxal and D-lactate in urine to evaluate saikosaponin C treatment in mice with accelerated nephrotoxic serum nephritis

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