Time Courses of Cortical Glucose Metabolism and Microglial Activity Across the Life-Span of Wild-Type Mice: A PET Study

Abstract

Contrary to findings in human brain, [¹⁸F]-FDG PET shows cerebral hypermetabolism of aged wild-type (WT) mice relative to younger animals, supposedly due to microglial activation. Therefore, we used dual tracer µPET to examine directly the link between neuroinflammation and hypermetabolism in aged mice. Methods: WT mice (5-20 months) were investigated in a cross-sectional design using [¹⁸F]-FDG (N = 43) and TSPO ([¹⁸F]-GE180; N = 58) µPET, with volume-of-interest and voxel-wise analyses. Biochemical analysis of plasma cytokine levels and immunohistochemical confirmation of microglial activity were also performed. Results: Age-dependent cortical hypermetabolism in WT mice relative to young animals aged five months peaked at 14.5 months (+16%,p<0.001), and declined to baseline at 20 months. Similarly, cortical TSPO binding increased to a maximum at 14.5 months (+15%, p<0.001), and remained high to 20 months, resulting in an overall correlation between [¹⁸F]-FDG uptake and TSPO binding (β=0.61; p<0.05). Biochemical and immunohistochemical analyses confirmed the TSPO µPET findings. Conclusion: Age-dependent neuroinflammation is associated with the controversial observation of cerebral hypermetabolism in aging WT mice.