Differences in in vitro microglial accumulation of the energy metabolism tracers [18F]FDG and [18F]BCPP-EF during LPS- and IL4 stimulation

Abstract The positron emission tomography probes 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and 2-tert-butyl-4-chloro-5-{6-[2-(2-[18F]fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([18F]BCPP-EF) are designed to evaluate glycolysis and oxidative phosphorylation, respectively, and are...

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Autores principales:	Chie Suzuki, Sarina Han, Gandhervin Kesavamoorthy, Mutsumi Kosugi, Kaori Araki, Norihiro Harada, Masakatsu Kanazawa, Hideo Tsukada, Yasuhiro Magata, Yasuomi Ouchi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/19461eedfa4b4b40ba27aa860c1c7720
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spelling	oai:doaj.org-article:19461eedfa4b4b40ba27aa860c1c77202021-12-02T18:02:49ZDifferences in in vitro microglial accumulation of the energy metabolism tracers [18F]FDG and [18F]BCPP-EF during LPS- and IL4 stimulation10.1038/s41598-021-92436-02045-2322https://doaj.org/article/19461eedfa4b4b40ba27aa860c1c77202021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92436-0https://doaj.org/toc/2045-2322Abstract The positron emission tomography probes 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and 2-tert-butyl-4-chloro-5-{6-[2-(2-[18F]fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([18F]BCPP-EF) are designed to evaluate glycolysis and oxidative phosphorylation, respectively, and are both used to estimate neuronal activity. However, previous studies have shown a discrepancy in these probes’ accumulation in the compromised region, possibly due to the presence of activated microglia acting like deleterious or neuroprotective phenotypes. Hence, we evaluated lipopolysaccharide (LPS)- and interleukin 4 (IL4)-stimulated microglial uptake of [14C]2DG and [18F]BCPP-EF to give a new insight into the hypothesis that different uptake of [18F]FDG and [18F]BCPP-EF can be ascribed to the different metabolic pathways activated during microglial activation. LPS or IL4 stimulation increased the proinflammatory or anti-inflammatory marker gene expression in microglial cells. In LPS-stimulated cells, [14C]2DG uptake and glycolysis related gene expression were elevated, and [18F]BCPP-EF uptake was reduced. In IL4-stimulated cells, [18F]BCPP-EF uptake was increased, and [14C]2DG uptake was decreased. The expression of genes involved in glycolysis and mitochondrial complex I subunits was not changed by IL4 stimulation. The uptake of [14C]2DG and [18F]BCPP-EF differs in LPS- and IL4-stimulated polarized microglial cells. The present results suggest that the in vivo accumulation of metabolic tracers [18F]FDG and [18F]BCPP-EF can be influenced by the different aspects of neuroinflammation.Chie SuzukiSarina HanGandhervin KesavamoorthyMutsumi KosugiKaori ArakiNorihiro HaradaMasakatsu KanazawaHideo TsukadaYasuhiro MagataYasuomi OuchiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chie Suzuki Sarina Han Gandhervin Kesavamoorthy Mutsumi Kosugi Kaori Araki Norihiro Harada Masakatsu Kanazawa Hideo Tsukada Yasuhiro Magata Yasuomi Ouchi Differences in in vitro microglial accumulation of the energy metabolism tracers [18F]FDG and [18F]BCPP-EF during LPS- and IL4 stimulation
description	Abstract The positron emission tomography probes 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and 2-tert-butyl-4-chloro-5-{6-[2-(2-[18F]fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([18F]BCPP-EF) are designed to evaluate glycolysis and oxidative phosphorylation, respectively, and are both used to estimate neuronal activity. However, previous studies have shown a discrepancy in these probes’ accumulation in the compromised region, possibly due to the presence of activated microglia acting like deleterious or neuroprotective phenotypes. Hence, we evaluated lipopolysaccharide (LPS)- and interleukin 4 (IL4)-stimulated microglial uptake of [14C]2DG and [18F]BCPP-EF to give a new insight into the hypothesis that different uptake of [18F]FDG and [18F]BCPP-EF can be ascribed to the different metabolic pathways activated during microglial activation. LPS or IL4 stimulation increased the proinflammatory or anti-inflammatory marker gene expression in microglial cells. In LPS-stimulated cells, [14C]2DG uptake and glycolysis related gene expression were elevated, and [18F]BCPP-EF uptake was reduced. In IL4-stimulated cells, [18F]BCPP-EF uptake was increased, and [14C]2DG uptake was decreased. The expression of genes involved in glycolysis and mitochondrial complex I subunits was not changed by IL4 stimulation. The uptake of [14C]2DG and [18F]BCPP-EF differs in LPS- and IL4-stimulated polarized microglial cells. The present results suggest that the in vivo accumulation of metabolic tracers [18F]FDG and [18F]BCPP-EF can be influenced by the different aspects of neuroinflammation.
format	article
author	Chie Suzuki Sarina Han Gandhervin Kesavamoorthy Mutsumi Kosugi Kaori Araki Norihiro Harada Masakatsu Kanazawa Hideo Tsukada Yasuhiro Magata Yasuomi Ouchi
author_facet	Chie Suzuki Sarina Han Gandhervin Kesavamoorthy Mutsumi Kosugi Kaori Araki Norihiro Harada Masakatsu Kanazawa Hideo Tsukada Yasuhiro Magata Yasuomi Ouchi
author_sort	Chie Suzuki
title	Differences in in vitro microglial accumulation of the energy metabolism tracers [18F]FDG and [18F]BCPP-EF during LPS- and IL4 stimulation
title_short	Differences in in vitro microglial accumulation of the energy metabolism tracers [18F]FDG and [18F]BCPP-EF during LPS- and IL4 stimulation
title_full	Differences in in vitro microglial accumulation of the energy metabolism tracers [18F]FDG and [18F]BCPP-EF during LPS- and IL4 stimulation
title_fullStr	Differences in in vitro microglial accumulation of the energy metabolism tracers [18F]FDG and [18F]BCPP-EF during LPS- and IL4 stimulation
title_full_unstemmed	Differences in in vitro microglial accumulation of the energy metabolism tracers [18F]FDG and [18F]BCPP-EF during LPS- and IL4 stimulation
title_sort	differences in in vitro microglial accumulation of the energy metabolism tracers [18f]fdg and [18f]bcpp-ef during lps- and il4 stimulation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/19461eedfa4b4b40ba27aa860c1c7720
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Differences in in vitro microglial accumulation of the energy metabolism tracers [18F]FDG and [18F]BCPP-EF during LPS- and IL4 stimulation

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