Microglial activation states drive glucose uptake and FDG-PET alterations in neurodegenerative diseases

Xiang, Xianyuan; Wind, Karin; Wiedemann, Thomas; Blume, Tanja; Shi, Yuan; Briel, Nils; Beyer, Leonie; Biechele, Gloria; Eckenweber, Florian; Zatcepin, Artem; Lammich, Sven; Ribičić, Sara; Tahirović, Sabina; Willem, Michael; Deußing, Maximilian; Palleis, Carla; Rauchmann, Boris‐Stephan; Gildehaus, Franz-Josef; Lindner, Simon; Spitz, Charlotte; Franzmeier, Nicolai; Baumann, Karlheinz; Rominger, Axel; Bartenstein, Peter; Ziegler, Sibylle; Drzezga, Alexander; Respondek, Gesine; Büerger, Katharina; Perneczky, Robert; Levin, Johannes; Höglinger, Günter U.; Herms, Jochen; Haass, Christian; Brendel, Matthias

doi:10.1126/scitranslmed.abe5640

Cited by 162 publications

(141 citation statements)

References 74 publications

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“…[ 18 F]FDG accumulates in brain tissue according to facilitated transport and hexokinase-mediated phosphorylation. The uptake of [ 18 F]FDG also depends on the consumption of glucose by the astrocytes in interaction with neuronal function [1], on the transport mediated by the glucose transporter 1 (GLUT-1) across the blood-brain barrier [2], and possibly during pathological inflammatory conditions on microglial activation states [3]. Currently, [ 18 F]FDG-PET, which is widely available in Europe, is the most accurate in vivo method for the investigation of regional human brain metabolism in clinical settings.…”

Section: Introductionmentioning

confidence: 99%

EANM procedure guidelines for brain PET imaging using [18F]FDG, version 3

Guedj

Varrone

Boellaard

et al. 2021

Eur J Nucl Med Mol Imaging

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134

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The present procedural guidelines summarize the current views of the EANM Neuro-Imaging Committee (NIC). The purpose of these guidelines is to assist nuclear medicine practitioners in making recommendations, performing, interpreting, and reporting results of [18F]FDG-PET imaging of the brain. The aim is to help achieve a high-quality standard of [18F]FDG brain imaging and to further increase the diagnostic impact of this technique in neurological, neurosurgical, and psychiatric practice. The present document replaces a former version of the guidelines that have been published in 2009. These new guidelines include an update in the light of advances in PET technology such as the introduction of digital PET and hybrid PET/MR systems, advances in individual PET semiquantitative analysis, and current broadening clinical indications (e.g., for encephalitis and brain lymphoma). Further insight has also become available about hyperglycemia effects in patients who undergo brain [18F]FDG-PET. Accordingly, the patient preparation procedure has been updated. Finally, most typical brain patterns of metabolic changes are summarized for neurodegenerative diseases. The present guidelines are specifically intended to present information related to the European practice. The information provided should be taken in the context of local conditions and regulations.

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Section: Introductionmentioning

confidence: 99%

EANM procedure guidelines for brain PET imaging using [18F]FDG, version 3

Guedj

Varrone

Boellaard

et al. 2021

Eur J Nucl Med Mol Imaging

Self Cite

134

View full text Add to dashboard Cite

show abstract

“…NO production from microglia is reportedly dependent on glucose as an energy source [ 122 ]. However, the metabolic pathway of glucose as an energy source for microglial function remains largely unknown [ 123 , 124 , 125 ]. Energy metabolism in inflammatory M1 microglia is believed to shift from oxidative phosphorylation in mitochondria to the glycolytic system [ 126 , 127 , 128 ], suggesting that PPP flux, a shunt pathway of the glycolytic system, might be enhanced in inflammatory M1 microglia.…”

Section: Issues To Be Resolved In the Futurementioning

confidence: 99%

Neuroprotection and Disease Modification by Astrocytes and Microglia in Parkinson Disease

Takahashi

Mashima

2022

Antioxidants

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Oxidative stress and neuroinflammation are common bases for disease onset and progression in many neurodegenerative diseases. In Parkinson disease, which is characterized by the degeneration of dopaminergic neurons resulting in dopamine depletion, the pathogenesis differs between hereditary and solitary disease forms and is often unclear. In addition to the pathogenicity of alpha-synuclein as a pathological disease marker, the involvement of dopamine itself and its interactions with glial cells (astrocyte or microglia) have attracted attention. Pacemaking activity, which is a hallmark of dopaminergic neurons, is essential for the homeostatic maintenance of adequate dopamine concentrations in the synaptic cleft, but it imposes a burden on mitochondrial oxidative glucose metabolism, leading to reactive oxygen species production. Astrocytes provide endogenous neuroprotection to the brain by producing and releasing antioxidants in response to oxidative stress. Additionally, the protective function of astrocytes can be modified by microglia. Some types of microglia themselves are thought to exacerbate Parkinson disease by releasing pro-inflammatory factors (M1 microglia). Although these inflammatory microglia may further trigger the inflammatory conversion of astrocytes, microglia may induce astrocytic neuroprotective effects (A2 astrocytes) simultaneously. Interestingly, both astrocytes and microglia express dopamine receptors, which are upregulated in the presence of neuroinflammation. The anti-inflammatory effects of dopamine receptor stimulation are also attracting attention because the functions of astrocytes and microglia are greatly affected by both dopamine depletion and therapeutic dopamine replacement in Parkinson disease. In this review article, we will focus on the antioxidative and anti-inflammatory effects of astrocytes and their synergism with microglia and dopamine.

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“…2F,G). Recent study by Xiang et al (2021) showed that [ 18 F]FDG uptake reflected metabolism derived from microglia and that the increased [ 18 F]FDG might instead due to microglia activation.…”

Section: Metabolism Imagingmentioning

confidence: 99%

“… Brendel et al (2019) demonstrated a reduced [ 18 F]FDG uptake in brain of hTau mice compared to wild-type mice and that treatment using novel aggregation-inhibiting oligomer modulator Anle138b can rescue this reduction in [ 18 F]FDG measures at follow-up scan after treatment ( Figures 2F,G ). Recent study by Xiang et al (2021) showed that [ 18 F]FDG uptake reflected metabolism derived from microglia and that the increased [ 18 F]FDG might instead due to microglia activation.…”

Section: Metabolism Imagingmentioning

confidence: 99%

Positron Emission Tomography in Animal Models of Tauopathies

Cao

Kong

et al. 2022

Front. Aging Neurosci.

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The microtubule-associated protein tau (MAPT) plays an important role in Alzheimer’s disease and primary tauopathy diseases. The abnormal accumulation of tau contributes to the development of neurotoxicity, inflammation, neurodegeneration, and cognitive deficits in tauopathy diseases. Tau synergically interacts with amyloid-beta in Alzheimer’s disease leading to detrimental consequence. Thus, tau has been an important target for therapeutics development for Alzheimer’s disease and primary tauopathy diseases. Tauopathy animal models recapitulating the tauopathy such as transgenic, knock-in mouse and rat models have been developed and greatly facilitated the understanding of disease mechanisms. The advance in PET and imaging tracers have enabled non-invasive detection of the accumulation and spread of tau, the associated microglia activation, metabolic, and neurotransmitter receptor alterations in disease animal models. In vivo microPET studies on mouse or rat models of tauopathy have provided significant insights into the phenotypes and time course of pathophysiology of these models and allowed the monitoring of treatment targeting at tau. In this study, we discuss the utilities of PET and recently developed tracers for evaluating the pathophysiology in tauopathy animal models. We point out the outstanding challenges and propose future outlook in visualizing tau-related pathophysiological changes in brain of tauopathy disease animal models.

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Microglial activation states drive glucose uptake and FDG-PET alterations in neurodegenerative diseases

Abstract: FDG-PET shows that microglial activation might drive cerebral glucose uptake in mice and patients with AD.

Cited by 162 publications

References 74 publications

EANM procedure guidelines for brain PET imaging using [18F]FDG, version 3

EANM procedure guidelines for brain PET imaging using [18F]FDG, version 3

Neuroprotection and Disease Modification by Astrocytes and Microglia in Parkinson Disease

Positron Emission Tomography in Animal Models of Tauopathies

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