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Lipopolysaccharide-induced alteration of mitochondrial morphology induces a metabolic shift in microglia modulating the inflammatory response in vitro and in vivo

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Lipopolysaccharide-induced alteration of mitochondrial morphology induces a metabolic shift in microglia modulating the inflammatory response in vitro and in vivo. / Nair, Syam; Sobotka, Kristina S; Joshi, Pooja; Gressens, Pierre; Fleiss, Bobbi; Thornton, Claire; Mallard, Carina; Hagberg, Henrik.

In: Glia, Vol. 67, No. 6, 01.06.2019, p. 1047-1061.

Research output: Contribution to journalArticle

Harvard

Nair, S, Sobotka, KS, Joshi, P, Gressens, P, Fleiss, B, Thornton, C, Mallard, C & Hagberg, H 2019, 'Lipopolysaccharide-induced alteration of mitochondrial morphology induces a metabolic shift in microglia modulating the inflammatory response in vitro and in vivo', Glia, vol. 67, no. 6, pp. 1047-1061. https://doi.org/10.1002/glia.23587

APA

Nair, S., Sobotka, K. S., Joshi, P., Gressens, P., Fleiss, B., Thornton, C., Mallard, C., & Hagberg, H. (2019). Lipopolysaccharide-induced alteration of mitochondrial morphology induces a metabolic shift in microglia modulating the inflammatory response in vitro and in vivo. Glia, 67(6), 1047-1061. https://doi.org/10.1002/glia.23587

Vancouver

Nair S, Sobotka KS, Joshi P, Gressens P, Fleiss B, Thornton C et al. Lipopolysaccharide-induced alteration of mitochondrial morphology induces a metabolic shift in microglia modulating the inflammatory response in vitro and in vivo. Glia. 2019 Jun 1;67(6):1047-1061. https://doi.org/10.1002/glia.23587

Author

Nair, Syam ; Sobotka, Kristina S ; Joshi, Pooja ; Gressens, Pierre ; Fleiss, Bobbi ; Thornton, Claire ; Mallard, Carina ; Hagberg, Henrik. / Lipopolysaccharide-induced alteration of mitochondrial morphology induces a metabolic shift in microglia modulating the inflammatory response in vitro and in vivo. In: Glia. 2019 ; Vol. 67, No. 6. pp. 1047-1061.

Bibtex Download

@article{e4ef68ce1c094c878bcae960dbb5b972,
title = "Lipopolysaccharide-induced alteration of mitochondrial morphology induces a metabolic shift in microglia modulating the inflammatory response in vitro and in vivo",
abstract = "Accumulating evidence suggests that changes in the metabolic signature of microglia underlie their response to inflammation. We sought to increase our knowledge of how pro-inflammatory stimuli induce metabolic changes. Primary microglia exposed to lipopolysaccharide (LPS)-expressed excessive fission leading to more fragmented mitochondria than tubular mitochondria. LPS-mediated Toll-like receptor 4 (TLR4) activation also resulted in metabolic reprogramming from oxidative phosphorylation to glycolysis. Blockade of mitochondrial fission by Mdivi-1, a putative mitochondrial division inhibitor led to the reversal of the metabolic shift. Mdivi-1 treatment also normalized the changes caused by LPS exposure, namely an increase in mitochondrial reactive oxygen species production and mitochondrial membrane potential as well as accumulation of key metabolic intermediate of TCA cycle succinate. Moreover, Mdivi-1 treatment substantially reduced LPS induced cytokine and chemokine production. Finally, we showed that Mdivi-1 treatment attenuated expression of genes related to cytotoxic, repair, and immunomodulatory microglia phenotypes in an in vivo neuroinflammation paradigm. Collectively, our data show that the activation of microglia to a classically pro-inflammatory state is associated with a switch to glycolysis that is mediated by mitochondrial fission, a process which may be a pharmacological target for immunomodulation.",
author = "Syam Nair and Sobotka, {Kristina S} and Pooja Joshi and Pierre Gressens and Bobbi Fleiss and Claire Thornton and Carina Mallard and Henrik Hagberg",
note = "{\textcopyright} 2019 Wiley Periodicals, Inc.",
year = "2019",
month = jun,
day = "1",
doi = "10.1002/glia.23587",
language = "English",
volume = "67",
pages = "1047--1061",
journal = "Glia",
issn = "0894-1491",
number = "6",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Lipopolysaccharide-induced alteration of mitochondrial morphology induces a metabolic shift in microglia modulating the inflammatory response in vitro and in vivo

AU - Nair, Syam

AU - Sobotka, Kristina S

AU - Joshi, Pooja

AU - Gressens, Pierre

AU - Fleiss, Bobbi

AU - Thornton, Claire

AU - Mallard, Carina

AU - Hagberg, Henrik

N1 - © 2019 Wiley Periodicals, Inc.

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Accumulating evidence suggests that changes in the metabolic signature of microglia underlie their response to inflammation. We sought to increase our knowledge of how pro-inflammatory stimuli induce metabolic changes. Primary microglia exposed to lipopolysaccharide (LPS)-expressed excessive fission leading to more fragmented mitochondria than tubular mitochondria. LPS-mediated Toll-like receptor 4 (TLR4) activation also resulted in metabolic reprogramming from oxidative phosphorylation to glycolysis. Blockade of mitochondrial fission by Mdivi-1, a putative mitochondrial division inhibitor led to the reversal of the metabolic shift. Mdivi-1 treatment also normalized the changes caused by LPS exposure, namely an increase in mitochondrial reactive oxygen species production and mitochondrial membrane potential as well as accumulation of key metabolic intermediate of TCA cycle succinate. Moreover, Mdivi-1 treatment substantially reduced LPS induced cytokine and chemokine production. Finally, we showed that Mdivi-1 treatment attenuated expression of genes related to cytotoxic, repair, and immunomodulatory microglia phenotypes in an in vivo neuroinflammation paradigm. Collectively, our data show that the activation of microglia to a classically pro-inflammatory state is associated with a switch to glycolysis that is mediated by mitochondrial fission, a process which may be a pharmacological target for immunomodulation.

AB - Accumulating evidence suggests that changes in the metabolic signature of microglia underlie their response to inflammation. We sought to increase our knowledge of how pro-inflammatory stimuli induce metabolic changes. Primary microglia exposed to lipopolysaccharide (LPS)-expressed excessive fission leading to more fragmented mitochondria than tubular mitochondria. LPS-mediated Toll-like receptor 4 (TLR4) activation also resulted in metabolic reprogramming from oxidative phosphorylation to glycolysis. Blockade of mitochondrial fission by Mdivi-1, a putative mitochondrial division inhibitor led to the reversal of the metabolic shift. Mdivi-1 treatment also normalized the changes caused by LPS exposure, namely an increase in mitochondrial reactive oxygen species production and mitochondrial membrane potential as well as accumulation of key metabolic intermediate of TCA cycle succinate. Moreover, Mdivi-1 treatment substantially reduced LPS induced cytokine and chemokine production. Finally, we showed that Mdivi-1 treatment attenuated expression of genes related to cytotoxic, repair, and immunomodulatory microglia phenotypes in an in vivo neuroinflammation paradigm. Collectively, our data show that the activation of microglia to a classically pro-inflammatory state is associated with a switch to glycolysis that is mediated by mitochondrial fission, a process which may be a pharmacological target for immunomodulation.

UR - http://www.scopus.com/inward/record.url?scp=85059962901&partnerID=8YFLogxK

U2 - 10.1002/glia.23587

DO - 10.1002/glia.23587

M3 - Article

C2 - 30637805

VL - 67

SP - 1047

EP - 1061

JO - Glia

JF - Glia

SN - 0894-1491

IS - 6

ER -

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