18F-Fluorodeoxyglucose Positron Emission Tomography Tracks the Heterogeneous Brain Susceptibility to the Hyperglycemia-Related Redox Stress

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

Research output: Contribution to journalArticlepeer-review

Abstract

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 (n = 17) or 150 mg/kg streptozotocin (n = 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.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume21
Issue number21
DOIs
Publication statusPublished - Oct 31 2020

Keywords

  • brain glucose metabolism
  • FDG-PET
  • hyperglycemia
  • oxidative stress
  • reticular pentose phosphate pathway

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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