Differences in in Vitro Microglial Accumulation of the Energy Metabolism Tracers [F]FDG and [F]BCPP-EF During LPS- and IL4 Stimulation

Overview

Journal Sci Rep

Specialty Science

Date 2021 Jun 25

PMID 34168190

Citations 6

Authors

Chie Suzuki

Sarina Han

Gandhervin Kesavamoorthy

Mutsumi Kosugi

Kaori Araki

Norihiro Harada

Masakatsu Kanazawa

Hideo Tsukada

Yasuhiro Magata

Yasuomi Ouchi

Affiliations

Soon will be listed here.

Abstract

The positron emission tomography probes 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) and 2-tert-butyl-4-chloro-5-{6-[2-(2-[F]fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([F]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 [C]2DG and [F]BCPP-EF to give a new insight into the hypothesis that different uptake of [F]FDG and [F]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, [C]2DG uptake and glycolysis related gene expression were elevated, and [F]BCPP-EF uptake was reduced. In IL4-stimulated cells, [F]BCPP-EF uptake was increased, and [C]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 [C]2DG and [F]BCPP-EF differs in LPS- and IL4-stimulated polarized microglial cells. The present results suggest that the in vivo accumulation of metabolic tracers [F]FDG and [F]BCPP-EF can be influenced by the different aspects of neuroinflammation.

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