Abstract
Brain aging is associated with changes of various metabolic pathways. Copper is required for brain development and function, but little is known about changes in copper metabolism during brain aging. The objective of this study was to investigate alteration of copper fluxes in the aging mouse brain with positron emission tomography/computed tomography using 64CuCl2 as a radiotracer (64CuCl2-PET/CT). A longitudinal study was conducted in C57BL/6 mice (n = 5) to measure age-dependent brain and whole-body changes of 64Cu radioactivity using PET/CT after oral administration of 64CuCl2 as a radiotracer. Cerebral 64Cu uptake at 13 months of age (0.17 ± 0.05 %ID/g) was higher than the cerebral 64Cu uptake at 5 months of age (0.11 ± 0.06 %ID/g, p < 0.001), followed by decrease to (0.14 ± 0.04 %ID/g, p = 0.02) at 26 months of age. In contrast, cerebral 18F-FDG uptake was highest at 5 months of age (7.8 ± 1.2 %ID/g) and decreased to similar values at 12 (5.2 ± 1.1 %ID/g, p < 0.001) and 22 (5.6 ± 1.1 %ID/g, p < 0.001) months of age. The findings demonstrated alteration of copper fluxes associated with brain aging and the time course of brain changes in copper fluxes differed from changes in brain glucose metabolism across time, suggesting independent underlying physiological processes. Hence, age-dependent changes of cerebral copper fluxes might represent a novel metabolic biomarker for assessment of human brain aging process with PET/CT using 64CuCl2 as a radiotracer.
Highlights
Brain is a dynamic organ with changes of various metabolic pathways in adaptation to aging process [1]
Brain aging is characterized by decline of glucose metabolism, predominantly in the prefrontal cortex [2, 3]. 2-deoxy-2-[F-18]-fluoro-Dglucose (18F-FDG) positron emission tomograph (PET) is a useful tool for assessment of brain glucose metabolism, but use of 18F-FDG PET for differentiation of healthy brain aging from pathological brain aging is sometimes limited by normal variation of brain glucose metabolism and other confounding factors such as drug effects [4]
Regions were shown for cerebellum (CB), Thalamus (T), olfactory bulb (OB), posterior cortex (PC), and frontal cortex (FC)
Summary
Brain is a dynamic organ with changes of various metabolic pathways in adaptation to aging process [1]. Age-dependent changes of 64Cu radioactivity were detected in the brains of Atp7b-/knockout mouse model of WD with PET/CT [25] Using this new 64CuCl2-PET/CT technique as a tool, this study aimed to conduct a longitudinal PET study to assess agedependent changes of copper fluxes in the brains of C57BL/6 mice. A concurrent longitudinal PET study using 18F-FDG) as a radiotracer [26] was performed to compare changes of copper fluxes with changes of glucose metabolism in mouse brain with aging The findings of this pilot PET study for the first time demonstrated age-dependent changes of 64Cu radioactivity in the brains of mice orally administered with 64CuCl2 as a radiotracer, supporting potential use of cerebral 64Cu uptake as a biomarker for noninvasive assessment of brain aging and age-related neurodegenerative disorders using 64CuCl2-PET/CT as a tool
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