Brain and Brown Adipose Tissue Metabolism in Transgenic Tg2576 Mice Models of Alzheimer Disease Assessed Using ¹⁸F-FDG PET Imaging.

IF 2.2 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS

Molecular Imaging Pub Date : 2017-01-01 DOI:10.1177/1536012117704557

Robert A Coleman, Christopher Liang, Rima Patel, Sarah Ali, Jogeshwar Mukherjee

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Abstract

Objective: Imaging animal models of Alzheimer disease (AD) is useful for the development of therapeutic drugs and understanding AD. Transgenic Swedish hAPPswe Tg2576 mice are a good model of β-amyloid plaques. We report ¹⁸F-fluoro-2-deoxyglucose (¹⁸F-FDG) positron emission tomography (PET) imaging of brain and intrascapular brown adipose tissue (IBAT) in transgenic mice 2576 (Tg2576) and wild-type (WT) mice.

Methods: Transgenic Tg2576 mice and WT mice, >18 months were injected intraperitonally with ≈ 25 to 30 MBq ¹⁸F-FDG while awake. After 60 minutes, they were anesthetized with isoflurane (2.5%) and imaged with Inveon MicroPET. Select mice were killed, imaged ex vivo, and 20 µm sections cut for autoradiography. ¹⁸F-FDG uptake in brain and IBAT PET and brain autoradiographs were analyzed.

Results: Fasting blood glucose levels averaged 120 mg/dL for WT and 100 mg/dL for Tg2576. Compared to WT, Tg2576 mice exhibited a decrease in SUVglc in the various brain regions. Average reductions in the cerebrum regions were as high as -20%, while changes in cerebellum were -3%. Uptake of ¹⁸F-FDG in IBAT decreased by -60% in Tg2576 mice and was found to be significant. Intrascapular brown adipose tissue findings in Tg2576 mice are new and not previously reported. Use of blood glucose for PET data analysis and corpus callosum as reference region for autoradiographic analysis were important to detect change in Tg2576 mice.

Conclusion: Our results suggest that ¹⁸F-FDG uptake in the Tg2576 mice brain show ¹⁸F-FDG deficits only when blood glucose is taken into consideration.

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利用 18F-FDG PET 成像评估阿尔茨海默病转基因 Tg2576 小鼠模型的大脑和棕色脂肪组织代谢。

目的：对阿尔茨海默病（AD）动物模型进行成像有助于开发治疗药物和了解阿尔茨海默病。转基因瑞典 hAPPswe Tg2576 小鼠是一种良好的 β 淀粉样蛋白斑块模型。我们报告了转基因小鼠2576（Tg2576）和野生型（WT）小鼠大脑和筋膜内棕色脂肪组织（IBAT）的18F-氟-2-脱氧葡萄糖（18F-FDG）正电子发射断层扫描（PET）成像：方法：清醒状态下，向大于18个月的转基因Tg2576小鼠和WT小鼠腹腔内注射≈25至30 MBq 18F-FDG。60 分钟后，用异氟烷（2.5%）麻醉，并用 Inveon MicroPET 进行成像。选择的小鼠被杀死，进行体外成像，并切割 20 µm 的切片进行自动放射成像。对大脑中的 18F-FDG 摄取、IBAT PET 和大脑自动放射图进行分析：结果：WT 和 Tg2576 的空腹血糖水平平均为 120 mg/dL，Tg2576 为 100 mg/dL。与 WT 小鼠相比，Tg2576 小鼠各脑区的 SUVglc 均有所下降。大脑区域的平均降幅高达-20%，而小脑的变化为-3%。在 Tg2576 小鼠中，IBAT 对 18F-FDG 的摄取量下降了-60%，而且下降幅度很大。Tg2576小鼠筋膜内棕色脂肪组织的发现是新发现，以前从未报道过。使用血糖进行 PET 数据分析以及将胼胝体作为自显影分析的参考区域对于检测 Tg2576 小鼠的变化非常重要：我们的研究结果表明，只有在考虑血糖的情况下，Tg2576 小鼠大脑中的 18F-FDG 摄取才会出现 18F-FDG 缺陷。

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来源期刊

Molecular Imaging Biochemistry, Genetics and Molecular Biology-Biotechnology

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3.60%

发文量

期刊介绍： Molecular Imaging is a peer-reviewed, open access journal highlighting the breadth of molecular imaging research from basic science to preclinical studies to human applications. This serves both the scientific and clinical communities by disseminating novel results and concepts relevant to the biological study of normal and disease processes in both basic and translational studies ranging from mice to humans.