Functional Brain Imaging in the Resting State and during Activation in Alzheimer's Disease: Implications for Disease Mechanisms Involving Oxidative Phosphorylation

Rapoport, Stanley I.

doi:10.1111/j.1749-6632.1999.tb07823.x

Cited by 41 publications

(29 citation statements)

References 66 publications

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“…How can these observations be reconciled with our data showing increased astrocytic glucose metabolism? A current explanation for the decrease of glucose metabolism in AD is that glucose utilization by neural cells in the affected brain areas is impaired (Blass, 2001;Gibson, 2002), as supported by observations of deficient activity of some enzymes involved in energy metabolism in AD brain extracts (Rapoport, 1999;Blass et al, 2000;Liang et al, 2008). In contrast, other reports have described an increase in the activity of enzymes linked to glucose metabolism (Bigl et al, 1999;Soucek et al, 2003).…”

mentioning

confidence: 73%

Amyloid-β Aggregates Cause Alterations of Astrocytic Metabolic Phenotype: Impact on Neuronal Viability

Allaman

Gavillet²,

Bélanger³

et al. 2010

J. Neurosci.

248

209

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Amyloid-␤(A␤)peptidesplayakeyroleinthepathogenesisofAlzheimer'sdiseaseandexertvarioustoxiceffectsonneurons;however,relatively littleisknownabouttheirinfluenceonglialcells.Astrocytesplayapivotalroleinbrainhomeostasis,contributingtotheregulationoflocalenergy metabolism and oxidative stress defense, two aspects of importance for neuronal viability and function. In the present study, we explored the effects of A␤ peptides on glucose metabolism in cultured astrocytes. Following A␤ 25-35 exposure, we observed an increase in glucose uptake and its various metabolic fates, i.e., glycolysis (coupled to lactate release), tricarboxylic acid cycle, pentose phosphate pathway, and incorporation into glycogen. A␤ increased hydrogen peroxide production as well as glutathione release into the extracellular space without affecting intracellular glutathione content. A causal link between the effects of A␤ on glucose metabolism and its aggregation and internalization into astrocytes through binding to members of the class A scavenger receptor family could be demonstrated. Using astrocyte-neuron cocultures, we observed that the overall modifications of astrocyte metabolism induced by A␤ impair neuronal viability. The effects of the A␤ 25-35 fragment were reproduced by A␤ 1-42 but not by A␤ 1-40 . Finally, the phosphoinositide 3-kinase (PI3-kinase) pathway appears to be crucial in these events since both the changes in glucose utilization and the decrease in neuronal viability are prevented by LY294002, a PI3-kinase inhibitor. This set of observations indicates that A␤ aggregation and internalization into astrocytes profoundly alter their metabolic phenotype with deleterious consequences for neuronal viability.

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mentioning

confidence: 73%

Amyloid-β Aggregates Cause Alterations of Astrocytic Metabolic Phenotype: Impact on Neuronal Viability

Allaman

Gavillet²,

Bélanger³

et al. 2010

J. Neurosci.

248

209

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“…This is because of the large number of clinical conditions that are accompanied by disturbed coupling of neural activity and CBF/BOLD, e.g., migraine, stroke, and Alzheimer's disease (Olesen et al, 1981;Nelles et al, 1999;Rapoport, 1999). These findings can be reproduced in experimental disease models.…”

Section: Deactivationmentioning

confidence: 99%

Brain Function and Neurophysiological Correlates of Signals Used in Functional Neuroimaging

2003

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“…18 F-2-fluoro-2-deoxy-D-glucose ( 18 FDG) is a tracer of cellular energy metabolism. It has been used extensively to monitor the metabolic activity of cells in vivo in the brain [2][3][4][5] and to detect tumours [6][7][8]. 18 FDG differs from glucose by the substitution of the hydroxyl group with a fluorine atom on the second carbon of the glucose.…”

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confidence: 99%

Uptake of¹⁸fluorodeoxyglucose in the cystic fibrosis lung: a measure of lung inflammation?

Labiris¹,

Nahmias²,

Freitag³

et al. 2003

Eur Respir J

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Positron emission tomography is a three-dimensional imaging technique that measures physiological effects, including metabolism. 18 Fluorodeoxyglucose has been extensively used as a tracer of cellular energy metabolism in the brain and in tumour detection. As neutrophils utilise glucose as an energy source during their respiratory burst, it was hypothesised that 18 fluorodeoxyglucose uptake, by these cells, could be interpreted as a measure of neutrophil activation in cystic fibrosis (CF).Ten adult CF patients were given a bolus intravenous injection of 18 fluorodeoxyglucose, followed by a 90-min dynamic mid-lung acquisition scan. Right-lung 18 fluorodeoxyglucose uptake was assessed using a Patlak plot and values were converted to glucose utilisation. Three clinically inactive pulmonary sarcoidosis patients served as controls.From the 10 CF patients with baseline sputum neutrophils of 14610 6 cells?mL -1 who were investigated, seven were found to have sputum at a normal or slightly depressed glucose utilisation rate (mean 1.33 mmol?g Positron emission tomography (PET) is a powerful, quantitative, nuclear medicine tomographic imaging technique. PET can be used to measure physiological effects such as blood flow, metabolism, ventilation, receptor occupancy, regional dose delivery and pharmacokinetics of radiolabelled drugs [1]. It combines principles of image reconstruction from projections with the use of specific biological molecules labelled with positron-emitting radioisotopes ( 11 C, 18 F, 15 O, 13 N) allowing regional measurements of dynamic processes to be taken. 18 FDG differs from glucose by the substitution of the hydroxyl group with a fluorine atom on the second carbon of the glucose. When injected intravenously, 18 FDG rapidly diffuses into the extracellular spaces throughout the body. It is transported into living cells by the same mechanism as glucose, via the D-glucose transporter and is phosphorylated by hexokinase to fluoro-deoxyglucose-6-phosphate. The deoxy substitution at the second carbon position prevents further metabolism and the product accumulates in the cell at a rate that reflects glucose metabolism. Increased glucose consumption is assumed to lead to an increased rate of tracer uptake. The rate of accumulation of 18 FDG in tissue after intravenous injection reflects the combined transport and hexokinase activity in the cells [9].18 FDG-PET studies of the lung are still relatively few compared with the number of oncological, neurological and cardiac studies.The inflammatory process, in particular neutrophils, has been implicated in the pathogenesis of a variety of lung diseases including cystic fibrosis (CF), bronchiectasis, and chronic bronchitis. Neutrophils contribute to pulmonary destruction by production and release of cytotoxic enzymes (e.g. elastase, myeloperoxidase) and toxic oxygen metabolites [10]. Markers of inflammation in blood, bronchoalveolar lavage (BAL), sputum and lung biopsy serve as indirect measurements of inflammation, making the detection of re...

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Functional Brain Imaging in the Resting State and during Activation in Alzheimer's Disease: Implications for Disease Mechanisms Involving Oxidative Phosphorylation

Cited by 41 publications

References 66 publications

Amyloid-β Aggregates Cause Alterations of Astrocytic Metabolic Phenotype: Impact on Neuronal Viability

Amyloid-β Aggregates Cause Alterations of Astrocytic Metabolic Phenotype: Impact on Neuronal Viability

Brain Function and Neurophysiological Correlates of Signals Used in Functional Neuroimaging

Uptake of¹⁸fluorodeoxyglucose in the cystic fibrosis lung: a measure of lung inflammation?

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Functional Brain Imaging in the Resting State and during Activation in Alzheimer's Disease: Implications for Disease Mechanisms Involving Oxidative Phosphorylation

Cited by 41 publications

References 66 publications

Amyloid-β Aggregates Cause Alterations of Astrocytic Metabolic Phenotype: Impact on Neuronal Viability

Amyloid-β Aggregates Cause Alterations of Astrocytic Metabolic Phenotype: Impact on Neuronal Viability

Brain Function and Neurophysiological Correlates of Signals Used in Functional Neuroimaging

Uptake of18fluorodeoxyglucose in the cystic fibrosis lung: a measure of lung inflammation?

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Uptake of¹⁸fluorodeoxyglucose in the cystic fibrosis lung: a measure of lung inflammation?