18F-Fluorodeoxyglucose Positron Emission Tomography Tracks the Heterogeneous Brain Susceptibility to the Hyperglycemia-Related Redox Stress.
Alberto MiceliVanessa CossuCecilia MariniPatrizia CastellaniStefano RaffaMaria Isabella DoneganiSilvia BrunoSilvia RaveraLaura EmioniteAnna Maria OrengoFederica GrilloFlavio NobiliSilvia MorbelliAntonio UccelliGianmario SambucetiMatteo BaucknehtPublished in: International journal of molecular sciences (2020)
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.
Keyphrases
- positron emission tomography
- diabetic rats
- computed tomography
- endoplasmic reticulum
- pet ct
- pet imaging
- resting state
- oxidative stress
- white matter
- end stage renal disease
- functional connectivity
- cerebral ischemia
- ejection fraction
- chronic kidney disease
- high fat diet induced
- high resolution
- newly diagnosed
- peritoneal dialysis
- estrogen receptor
- mild cognitive impairment
- high fat diet
- machine learning
- insulin resistance
- artificial intelligence
- big data
- skeletal muscle
- photodynamic therapy
- drug induced
- anti inflammatory
- fluorescence imaging
- patient reported