18F-Fluorodeoxyglucose Positron Emission Tomography Tracks the Heterogeneous Brain Susceptibility to the Hyperglycemia-Related Redox Stress
In cognitively normal patients, mild hyperglycemia selectively decreases 18F-Fluorodeoxyglucose (FDG) uptake in the posterior brain, reproducing Alzheimer disease pattern, hampering the diagnostic accuracy of this widely used tool. This phenomenon might involve either a heterogeneous response of glu...
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doaj-4d2fc5d426bc4482bc0cf645921018462020-11-25T03:56:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-01218154815410.3390/ijms2121815418F-Fluorodeoxyglucose Positron Emission Tomography Tracks the Heterogeneous Brain Susceptibility to the Hyperglycemia-Related Redox StressAlberto Miceli0Vanessa Cossu1Cecilia Marini2Patrizia Castellani3Stefano Raffa4Maria Isabella Donegani5Silvia Bruno6Silvia Ravera7Laura Emionite8Anna Maria Orengo9Federica Grillo10Flavio Nobili11Silvia Morbelli12Antonio Uccelli13Gianmario Sambuceti14Matteo Bauckneht15Department of Health Sciences, University of Genoa, 16132 Genova, ItalyDepartment of Health Sciences, University of Genoa, 16132 Genova, ItalyNuclear Medicine, IRCCS Ospedale Policlinico San Martino, 16132 Genova, ItalyCell Biology, IRCCS Ospedale Policlinico San Martino, 16132 Genova, ItalyDepartment of Health Sciences, University of Genoa, 16132 Genova, ItalyDepartment of Health Sciences, University of Genoa, 16132 Genova, ItalyDepartment of Experimental Medicine, Human Anatomy, University of Genoa, 16132 Genova, ItalyDepartment of Experimental Medicine, Human Anatomy, University of Genoa, 16132 Genova, ItalyAnimal Facility, IRCCS Ospedale Policlinico San Martino, 16132 Genova, ItalyNuclear Medicine, IRCCS Ospedale Policlinico San Martino, 16132 Genova, ItalyDepartment of Surgical Sciences and Integrated Diagnostics, Pathology Unit, University of Genoa, 16132 Genova, ItalyDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Center of Excellence for Biomedical Research, University of Genoa, 16132 Genoa, ItalyDepartment of Health Sciences, University of Genoa, 16132 Genova, ItalyDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Center of Excellence for Biomedical Research, University of Genoa, 16132 Genoa, ItalyDepartment of Health Sciences, University of Genoa, 16132 Genova, ItalyNuclear Medicine, IRCCS Ospedale Policlinico San Martino, 16132 Genova, ItalyIn cognitively normal patients, mild hyperglycemia selectively decreases 18F-Fluorodeoxyglucose (FDG) uptake in the posterior brain, reproducing Alzheimer disease pattern, hampering the diagnostic accuracy of this widely used tool. This phenomenon might involve either a heterogeneous response of glucose metabolism or a different sensitivity to hyperglycemia-related redox stress. Indeed, previous studies reported a close link between FDG uptake and activation of a specific pentose phosphate pathway (PPP), triggered by hexose-6P-dehydrogenase (H6PD) and contributing to fuel NADPH-dependent antioxidant responses in the endoplasmic reticulum (ER). To clarify this issue, dynamic positron emission tomography was performed in 40 BALB/c mice four weeks after administration of saline (<i>n</i> = 17) or 150 mg/kg streptozotocin (<i>n</i> = 23, STZ). Imaging data were compared with biochemical and histological indexes of glucose metabolism and redox balance. Cortical FDG uptake was homogeneous in controls, while it was selectively decreased in the posterior brain of STZ mice. This difference was independent of the activity of enzymes regulating glycolysis and cytosolic PPP, while it was paralleled by a decreased H6PD catalytic function and enhanced indexes of oxidative damage. Thus, the relative decrease in FDG uptake of the posterior brain reflects a lower activation of ER-PPP in response to hyperglycemia-related redox stress in these areas.https://www.mdpi.com/1422-0067/21/21/8154brain glucose metabolismFDG-PEThyperglycemiaoxidative stressreticular pentose phosphate pathway |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alberto Miceli Vanessa Cossu Cecilia Marini Patrizia Castellani Stefano Raffa Maria Isabella Donegani Silvia Bruno Silvia Ravera Laura Emionite Anna Maria Orengo Federica Grillo Flavio Nobili Silvia Morbelli Antonio Uccelli Gianmario Sambuceti Matteo Bauckneht |
spellingShingle |
Alberto Miceli Vanessa Cossu Cecilia Marini Patrizia Castellani Stefano Raffa Maria Isabella Donegani Silvia Bruno Silvia Ravera Laura Emionite Anna Maria Orengo Federica Grillo Flavio Nobili Silvia Morbelli Antonio Uccelli Gianmario Sambuceti Matteo Bauckneht 18F-Fluorodeoxyglucose Positron Emission Tomography Tracks the Heterogeneous Brain Susceptibility to the Hyperglycemia-Related Redox Stress International Journal of Molecular Sciences brain glucose metabolism FDG-PET hyperglycemia oxidative stress reticular pentose phosphate pathway |
author_facet |
Alberto Miceli Vanessa Cossu Cecilia Marini Patrizia Castellani Stefano Raffa Maria Isabella Donegani Silvia Bruno Silvia Ravera Laura Emionite Anna Maria Orengo Federica Grillo Flavio Nobili Silvia Morbelli Antonio Uccelli Gianmario Sambuceti Matteo Bauckneht |
author_sort |
Alberto Miceli |
title |
18F-Fluorodeoxyglucose Positron Emission Tomography Tracks the Heterogeneous Brain Susceptibility to the Hyperglycemia-Related Redox Stress |
title_short |
18F-Fluorodeoxyglucose Positron Emission Tomography Tracks the Heterogeneous Brain Susceptibility to the Hyperglycemia-Related Redox Stress |
title_full |
18F-Fluorodeoxyglucose Positron Emission Tomography Tracks the Heterogeneous Brain Susceptibility to the Hyperglycemia-Related Redox Stress |
title_fullStr |
18F-Fluorodeoxyglucose Positron Emission Tomography Tracks the Heterogeneous Brain Susceptibility to the Hyperglycemia-Related Redox Stress |
title_full_unstemmed |
18F-Fluorodeoxyglucose Positron Emission Tomography Tracks the Heterogeneous Brain Susceptibility to the Hyperglycemia-Related Redox Stress |
title_sort |
18f-fluorodeoxyglucose positron emission tomography tracks the heterogeneous brain susceptibility to the hyperglycemia-related redox stress |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-10-01 |
description |
In cognitively normal patients, mild hyperglycemia selectively decreases 18F-Fluorodeoxyglucose (FDG) uptake in the posterior brain, reproducing Alzheimer disease pattern, hampering the diagnostic accuracy of this widely used tool. This phenomenon might involve either a heterogeneous response of glucose metabolism or a different sensitivity to hyperglycemia-related redox stress. Indeed, previous studies reported a close link between FDG uptake and activation of a specific pentose phosphate pathway (PPP), triggered by hexose-6P-dehydrogenase (H6PD) and contributing to fuel NADPH-dependent antioxidant responses in the endoplasmic reticulum (ER). To clarify this issue, dynamic positron emission tomography was performed in 40 BALB/c mice four weeks after administration of saline (<i>n</i> = 17) or 150 mg/kg streptozotocin (<i>n</i> = 23, STZ). Imaging data were compared with biochemical and histological indexes of glucose metabolism and redox balance. Cortical FDG uptake was homogeneous in controls, while it was selectively decreased in the posterior brain of STZ mice. This difference was independent of the activity of enzymes regulating glycolysis and cytosolic PPP, while it was paralleled by a decreased H6PD catalytic function and enhanced indexes of oxidative damage. Thus, the relative decrease in FDG uptake of the posterior brain reflects a lower activation of ER-PPP in response to hyperglycemia-related redox stress in these areas. |
topic |
brain glucose metabolism FDG-PET hyperglycemia oxidative stress reticular pentose phosphate pathway |
url |
https://www.mdpi.com/1422-0067/21/21/8154 |
work_keys_str_mv |
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