Time Courses of Cortical Glucose Metabolism and Microglial Activity Across the Life Span of Wild-Type Mice: A PET Study
Time Courses of Cortical Glucose Metabolism and Microglial Activity Across the Life Span of Wild-Type Mice: A PET Study
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DOI：
10.2967/jnumed.117.195107
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发表时间：
2017-12-01
影响因子：
9.3
通讯作者：
Rominger, Axel
中科院分区：
文献类型：
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作者：
Brendel, Matthias;Focke, Carola;Rominger, Axel
与人类大脑中的发现相反，F-18-FDG PET显示老年野生型（WT）小鼠相对于年轻动物的脑代谢亢进，推测是由于小胶质细胞活化。因此，我们使用双示踪小动物PET直接检查老年小鼠神经炎症和高代谢之间的联系。研究方法：采用F-18-FDG（n = 543）和转运蛋白（TSPO）（F-18-GE 180; n = 58）小动物PET，以横断面设计研究WT小鼠（5-20月龄），并进行感兴趣体积和体素分析。还进行了血浆细胞因子水平的生化分析和小胶质细胞活性的免疫组织化学确认。结果如下：相对于5月龄的年轻动物，WT小鼠中的皮质醇依赖性高代谢在14.5月龄时达到峰值（116%，P < 0.001），并在20月龄时下降至基线。同样，皮质TSPO结合在14.5个月时增加到最大值（115%，P < 0.001），并保持高水平至20个月，导致F-18-FDG摄取与TSPO结合之间的总体相关性（R = 0.69，P < 0.005）。生化和免疫组化分析证实了TSPO小动物PET结果。结论：衰老WT小鼠脑高代谢的争议性观察结果与神经元依赖性炎症有关。
Contrary to findings in the human brain, F-18-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 small-animal PET to examine directly the link between neuroinflammation and hypermetabolism in aged mice. Methods: WT mice (5-20 mo) were investigated in a cross-sectional design using F-18-FDG (n 5 43) and translocator protein (TSPO) (F-18-GE180; n = 58) small-animal PET, with volume-of-interest and voxelwise 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 5 mo peaked at 14.5 mo (116%, P < 0.001) and declined to baseline at 20 mo. Similarly, cortical TSPO binding increased to a maximum at 14.5 mo (115%, P < 0.001) and remained high to 20 mo, resulting in an overall correlation between F-18-FDG uptake and TSPO binding (R = 0.69, P < 0.005). Biochemical and immunohistochemical analyses confirmed the TSPO small-animal PET findings. Conclusion: Age-dependent neuroinflammation is associated with the controversial observation of cerebral hypermetabolism in aging WT mice.