[ (18) F]FDG PET/CT Studies in Transgenic Hualpha-Syn (A53T) Parkinson's Disease Mouse Model of α-Synucleinopathy.

[ (18) F]FDG PET/CT Studies in Transgenic Hualpha-Syn (A53T) Parkinson's Disease Mouse Model of α-Synucleinopathy.
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DOI:
10.3389/fnins.2021.676257
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发表时间:
2021
影响因子:
4.3
通讯作者:
Mukherjee J
Mukherjee J
中科院分区:
医学2区
文献类型:
--
作者:
Mondal R;Campoy AT;Liang C;Mukherjee J

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转基因小鼠品系M83表达A53T突变体α-突触核蛋白的水平是内源性小鼠α-突触核蛋白水平的6倍,是帕金森病(PD)中发现的α-突触核素病的模型。这种Hupha-Syn(A53T)PD模型可用于评估PD发病早期的非运动功能障碍。我们报告了使用[18F]FDG PET/CT在Hupha-Syn(A53T)PD小鼠模型中与非携带者小鼠相比的代谢变化的研究结果。雄性和雌性小鼠在3%异氟醚麻醉下注射[18F]FDG 2 h后进行全身PET/CT显像。脑图像与与小鼠脑MRI模板共同配准的PET图像进行分析。与未携带基因的小鼠相比,携带Hupha-Syn(A53T)基因的小鼠在多个脑区的[18F]FDG摄取量显著降低。9个月龄的A53T PD小鼠后肢肌肉和下脊髓[18F]FDG代谢明显降低,也是神经退行性疾病的征兆,进行性运动功能障碍导致死亡。在9月龄的雄性和雌性Hupha-Syn(A53)小鼠中,观察到[18F]FDG摄取显著减少(高达30%)。这与帕金森病患者的皮质低代谢相一致。因此,HUAlpha-Syn(A53)小鼠可能是发现新的生物标记物的PDα-突触核病相关研究的合适模型。
Transgenic mice line M83 that express the A53T mutant α–synuclein protein at six times the level of endogenous mice α–synuclein are a model of α-synucleinopathy found in Parkinson’s disease (PD). This Hualpha-Syn (A53T) PD model is useful in assessing non-motor deficits at earlier stages of onset of PD. We report findings on metabolic changes using [18F]FDG PET/CT in the Hualpha-Syn (A53T) PD mouse model in comparison to non-carrier mice. Whole-body PET/CT imaging of male and female mice were carried out 2 h after [18F]FDG ip administration under 3% isoflurane anesthesia. Brain images were analyzed with PET images coregistered to a mouse brain MRI template. Hualpha-Syn (A53T) mice had significantly lower [18F]FDG uptake in several brain regions compared to the no-carrier mice. Significant hind limb muscle and lower spinal cord [18F]FDG hypometabolism at 9 months of age in A53T PD mice was also indicative of neurodegenerative disease, with a progressive motoric dysfunction leading to death. Significant decrease (up to 30%) in [18F]FDG uptake were observed in 9-month old male and female Hualpha-Syn (A53) mice. This is consistent with the cortical hypometabolism in PD patients. Hualpha-Syn (A53) mice may thus be a suitable model for studies related to PD α-synucleinopathy for the discovery of new biomarkers.
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