Alteration of copper fluxes in brain aging: A longitudinal study in Rodent using 64CuCl2-PET/CT

Fangyu Peng, Fang Xie, Otto Muzik

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)109-118
Number of pages10
JournalAging and Disease
Volume9
Issue number1
DOIs
StatePublished - Feb 1 2018

Fingerprint

Longitudinal Studies
Copper
Rodentia
Brain
Physiological Phenomena
Fluorodeoxyglucose F18
Metabolic Networks and Pathways
Inbred C57BL Mouse
Radioactivity
Oral Administration
Biomarkers
Glucose

Keywords

  • Alzheimer's disease
  • Brain aging
  • Copper fluxes
  • Copper-64 chloride
  • Glucose metabolism
  • Positron emission tomography

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Geriatrics and Gerontology
  • Clinical Neurology
  • Cell Biology

Cite this

Alteration of copper fluxes in brain aging : A longitudinal study in Rodent using 64CuCl2-PET/CT. / Peng, Fangyu; Xie, Fang; Muzik, Otto.

In: Aging and Disease, Vol. 9, No. 1, 01.02.2018, p. 109-118.

Research output: Contribution to journalArticle

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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.",
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