PDF(Pubmed)
Abstract：
UNASSIGNED: The 5xFAD mouse is a popular model of familial Alzheimer\'s disease (AD) that is characterized by early beta-amyloid (Aβ) deposition and cognitive decrements. Despite numerous studies, the 5xFAD mouse has not been comprehensively phenotyped for vascular and metabolic perturbations over its lifespan.
UNASSIGNED: Male and female 5xFAD and wild type (WT) littermates underwent in vivo 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging at 4, 6, and 12 months of age to assess regional glucose metabolism. A separate cohort of mice (4, 8, 12 months) underwent \"vessel painting\" which labels all cerebral vessels and were analyzed for vascular characteristics such as vessel density, junction density, vessel length, network complexity, number of collaterals, and vessel diameter.
UNASSIGNED: With increasing age, vessels on the cortical surface in both 5xFAD and WT mice showed increased vessel length, vessel and junction densities. The number of collateral vessels between the middle cerebral artery (MCA) and the anterior and posterior cerebral arteries decreased with age but collateral diameters were significantly increased only in 5xFAD mice. MCA total vessel length and junction density were decreased in 5xFAD mice compared to WT at 4 months. Analysis of 18F-FDG cortical uptake revealed significant differences between WT and 5xFAD mice spanning 4-12 months. Broadly, 5xFAD males had significantly increased 18F-FDG uptake at 12 months compared to WT mice. In most cortical regions, female 5xFAD mice had reduced 18F-FDG uptake compared to WT across their lifespan.
UNASSIGNED: While the 5xFAD mouse exhibits AD-like cognitive deficits as early as 4 months of age that are associated with increasing Aβ deposition, we only found significant differences in cortical vascular features in males, not in females. Interestingly, 5xFAD male and female mice exhibited opposite effects in 18F-FDG uptake. The MCA supplies blood to large portions of the somatosensory cortex and portions of motor and visual cortex and increased vessel length alongside decreased collaterals which coincided with higher metabolic rates in 5xFAD mice. Thus, a potential mismatch between metabolic demand and vascular delivery of nutrients in the face of increasing Aβ deposition could contribute to the progressive cognitive deficits seen in the 5xFAD mouse model.
UNASSIGNED: Male and female 5xFAD and wild type (WT) littermates underwent in vivo 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging at 4, 6, and 12 months of age to assess regional glucose metabolism. A separate cohort of mice (4, 8, 12 months) underwent \"vessel painting\" which labels all cerebral vessels and were analyzed for vascular characteristics such as vessel density, junction density, vessel length, network complexity, number of collaterals, and vessel diameter.
UNASSIGNED: With increasing age, vessels on the cortical surface in both 5xFAD and WT mice showed increased vessel length, vessel and junction densities. The number of collateral vessels between the middle cerebral artery (MCA) and the anterior and posterior cerebral arteries decreased with age but collateral diameters were significantly increased only in 5xFAD mice. MCA total vessel length and junction density were decreased in 5xFAD mice compared to WT at 4 months. Analysis of 18F-FDG cortical uptake revealed significant differences between WT and 5xFAD mice spanning 4-12 months. Broadly, 5xFAD males had significantly increased 18F-FDG uptake at 12 months compared to WT mice. In most cortical regions, female 5xFAD mice had reduced 18F-FDG uptake compared to WT across their lifespan.
UNASSIGNED: While the 5xFAD mouse exhibits AD-like cognitive deficits as early as 4 months of age that are associated with increasing Aβ deposition, we only found significant differences in cortical vascular features in males, not in females. Interestingly, 5xFAD male and female mice exhibited opposite effects in 18F-FDG uptake. The MCA supplies blood to large portions of the somatosensory cortex and portions of motor and visual cortex and increased vessel length alongside decreased collaterals which coincided with higher metabolic rates in 5xFAD mice. Thus, a potential mismatch between metabolic demand and vascular delivery of nutrients in the face of increasing Aβ deposition could contribute to the progressive cognitive deficits seen in the 5xFAD mouse model.
摘要：
■5xFAD小鼠是家族性阿尔茨海默病（AD）的流行模型，其特征在于早期β-淀粉样蛋白（Aβ）沉积和认知功能下降。尽管有大量的研究,5xFAD小鼠在其寿命期内尚未进行血管和代谢扰动的全面表型分析。
■男性和女性5xFAD和野生型(WT)同窝在4、6和12月龄时进行体内18F-氟脱氧葡萄糖(FDG)正电子发射断层扫描(PET)成像以评估局部葡萄糖代谢。一组单独的小鼠（4，8，12个月）进行了“血管涂漆”，标记了所有脑血管，并分析了血管特征，例如血管密度，结密度,血管长度,网络复杂性，抵押品的数量，和血管直径。
■随着年龄的增长，5xFAD和WT小鼠皮质表面的血管显示血管长度增加，血管和结密度。大脑中动脉（MCA）与大脑前后动脉之间的侧支血管数量随着年龄的增长而减少，但侧支直径仅在5xFAD小鼠中显着增加。在4个月时,与WT相比,5xFAD小鼠中的MCA总血管长度和连接密度降低。18F-FDG皮层摄取的分析揭示了WT和5xFAD小鼠之间跨越4-12个月的显著差异。广义上,与WT小鼠相比,5xFAD雄性在12个月时具有显著增加的18F-FDG摄取。在大多数皮质区域，与WT相比,雌性5xFAD小鼠的18F-FDG摄取减少。
■虽然5xFAD小鼠早在4个月大时就表现出与Aβ沉积增加相关的AD样认知缺陷，我们只发现男性皮质血管特征存在显著差异，不是女性。有趣的是,5xFAD雄性和雌性小鼠在18F-FDG摄取中表现出相反的作用。MCA向大部分体感皮层以及运动和视觉皮层的一部分提供血液，并增加了血管长度以及减少的侧支，这与5xFAD小鼠的较高代谢率相吻合。因此，在Aβ沉积增加的情况下,代谢需求与血管营养输送之间的潜在不匹配可能导致5xFAD小鼠模型中出现的进行性认知缺陷.
■男性和女性5xFAD和野生型(WT)同窝在4、6和12月龄时进行体内18F-氟脱氧葡萄糖(FDG)正电子发射断层扫描(PET)成像以评估局部葡萄糖代谢。一组单独的小鼠（4，8，12个月）进行了“血管涂漆”，标记了所有脑血管，并分析了血管特征，例如血管密度，结密度,血管长度,网络复杂性，抵押品的数量，和血管直径。
■随着年龄的增长，5xFAD和WT小鼠皮质表面的血管显示血管长度增加，血管和结密度。大脑中动脉（MCA）与大脑前后动脉之间的侧支血管数量随着年龄的增长而减少，但侧支直径仅在5xFAD小鼠中显着增加。在4个月时,与WT相比,5xFAD小鼠中的MCA总血管长度和连接密度降低。18F-FDG皮层摄取的分析揭示了WT和5xFAD小鼠之间跨越4-12个月的显著差异。广义上,与WT小鼠相比,5xFAD雄性在12个月时具有显著增加的18F-FDG摄取。在大多数皮质区域，与WT相比,雌性5xFAD小鼠的18F-FDG摄取减少。
■虽然5xFAD小鼠早在4个月大时就表现出与Aβ沉积增加相关的AD样认知缺陷，我们只发现男性皮质血管特征存在显著差异，不是女性。有趣的是,5xFAD雄性和雌性小鼠在18F-FDG摄取中表现出相反的作用。MCA向大部分体感皮层以及运动和视觉皮层的一部分提供血液，并增加了血管长度以及减少的侧支，这与5xFAD小鼠的较高代谢率相吻合。因此，在Aβ沉积增加的情况下,代谢需求与血管营养输送之间的潜在不匹配可能导致5xFAD小鼠模型中出现的进行性认知缺陷.
