Abstract
Using positron emission tomography, we measured in vivo uptake of 18F-fluorodeoxyglucose (FDG) in the brain and heart of C57Bl/6 mice at intervals across a 24-hour light-dark cycle. Our data describe a significant, high amplitude rhythm in FDG uptake throughout the whole brain, peaking at the mid-dark phase of the light-dark cycle, which is the active phase for nocturnal mice. Under these conditions, heart FDG uptake did not vary with time of day, but did show biological variation throughout the 24-hour period for measurements within the same mice. FDG uptake was scanned at different times of day within an individual mouse, and also compared to different times of day between individuals, showing both biological and technical reproducibility of the 24-hour pattern in FDG uptake. Regional analysis of brain FDG uptake revealed especially high amplitude rhythms in the olfactory bulb and cortex, while low amplitude rhythms were observed in the amygdala, brain stem and hypothalamus. Low amplitude 24-hour rhythms in regional FDG uptake may be due to multiple rhythms with different phases in a single brain structure, quenching some of the amplitude. Our data show that the whole brain exhibits significant, high amplitude daily variation in glucose uptake in living mice. Reports applying the 2-deoxy-D[14C]-glucose method for the quantitative determination of the rates of local cerebral glucose utilization indicate only a small number of brain regions exhibiting a day versus night variation in glucose utilization. In contrast, our data show 24-hour patterns in glucose uptake in most of the brain regions examined, including several regions that do not show a difference in glucose utilization. Our data also emphasizes a methodological requirement of controlling for the time of day of scanning FDG uptake in the brain in both clinical and pre-clinical settings, and suggests waveform normalization of FDG measurements at different times of the day.
Highlights
Positron Emission Tomography (PET) is a non-invasive and quantitative nuclear imaging modality used for a range of clinical diagnostic and pre-clinical experimental applications
Because of the short half-life of the radionucleotide this introduces a peculiar dichotomy in which human patients are imaged during their ‘‘awake’’ phase of the day, while pre-clinical specimens like nocturnal mice are imaged during their ‘‘sleep’’ phase, unless they are kept under light-dark conditions that are different from the normal day timing
Both for brain and heart tissue, there was no effect of sex of the animal on the total FDG uptake
Summary
Positron Emission Tomography (PET) is a non-invasive and quantitative nuclear imaging modality used for a range of clinical diagnostic and pre-clinical experimental applications. FDG is taken up by cells and subsequently phosphorylated, but cannot be metabolized any further [2], providing a measure of glucose uptake by cells. This imaging technique provides functional information in detecting tissues with high glucose demands such as the heart, the brain, and many types of cancers. PET scanning is used in a wide array of pre-clinical and clinical settings to investigate of diseases such as dementia, Alzheimer’s disease, Parkinson’s disease, brain injury, stroke, coronary heart disease and oncology [3,4,5]. Because of the short half-life of the radionucleotide this introduces a peculiar dichotomy in which human patients are imaged during their ‘‘awake’’ phase of the day, while pre-clinical specimens like nocturnal mice are imaged during their ‘‘sleep’’ phase, unless they are kept under light-dark conditions that are different from the normal day timing
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