Assessment of glucose metabolism in a rat model of aging

Objectives Cognitive impairment is frequently observed in aging. In order to correlate alterations in cerebral glucose metabolism with age, we evaluated FDG-PET as a quantitative tool.

Methods Male brown Norway rats (300-350g) were used. For assessment of cognitive impairment, spatial memory was assessed using a Morris water maze. The mean proximity of animals to the platform was sampled. The path length before finding the platform was also measured. Rats of different ages were recruited for the PET study in group A (n=6, 3 months age) and group B (n=6, 25 months age). Briefly, overnight-fasted animals were injected with F-18-FDG (200 μCi, 0.5 ml) via tail vein. After 45 min of FDG uptake, the animals were anesthetized, a blood sample was withdrawn and the animals were imaged for 30 min. PET images were reconstructed by filtered back projection algorithm and processed using Amira software. Brain was segmented as a 3D region of interest, and standard FDG uptake was quantified.

Results The old rats had less spatial learning ability than the young rats as indicated by the shorter path lengths required to find the platform and the mean proximity to the platform in case of young rats. Quantitative analysis of PET images clearly showed that young animals take up and metabolize glucose significantly more than the old animals. The cerebral FDG uptake was 0.69% ± 0.06 and 0.39% ± 0.09 in young and old rats, respectively.

Conclusions There was correlation between cognitive impairment and reduced FDG uptake in brain. FDG-PET could be employed to evaluate changes in cerebral glucose metabolism as a function of aging and any therapeutic intervention