Vascular endothelial growth factor associated dissimilar cerebrovascular phenotypes in two different mouse models of Alzheimer's Disease.
Vascular endothelial growth factor associated dissimilar cerebrovascular phenotypes in two different mouse models of Alzheimer's Disease.
复制标题
DOI：
10.1016/j.neurobiolaging.2021.07.015
复制
发表时间：
2021-11
影响因子：
4.2
通讯作者：
Ahn HJ
中科院分区：
文献类型：
--
作者：
Tataryn NM;Singh V;Dyke JP;Berk-Rauch HE;Clausen DM;Aronowitz E;Norris EH;Strickland S;Ahn HJ
血管紊乱和脑代谢低下是阿尔茨海默病（AD）的重要组成部分。虽然已经设计了各种体内成像方式来检测AD患者和动物模型中的脑灌注和代谢的变化，但研究结果往往与成像技术和动物模型不同。因此，我们评估了两个流行的转基因AD小鼠品系，TgCRND8和5xFAD，在7个月和12个月的年龄在相同的条件下的脑灌注和葡萄糖代谢，并分析可能的分子机制异质性脑血管表型。结果显示，在这两种菌株不同的结果，显示AD进展的重要方面。TgCRND8小鼠在12月龄时显示出脑血流量和葡萄糖代谢显著降低，脑血容量（CBV）不变，而5xFAD小鼠在12月龄时显示出葡萄糖代谢不变，CBV显著增加，早期灌注不足的双相模式，随后在晚期疾病中反弹至正常脑血流量。最后，免疫印迹分析表明，VEGF依赖的血管张力变化可能会恢复正常灌注，并增加CBV在5xFAD。
Vascular perturbations and cerebral hypometabolism are emerging as important components of Alzheimer’s disease (AD). While various in vivo imaging modalities have been designed to detect changes of cerebral perfusion and metabolism in AD patients and animal models, study results were often heterogenous with respect to imaging techniques and animal models. We therefore evaluated cerebral perfusion and glucose metabolism of two popular transgenic AD mouse strains, TgCRND8 and 5xFAD, at 7 and 12 months-of-age under identical conditions and analyzed possible molecular mechanisms underlying heterogeneous cerebrovascular phenotypes. Results revealed disparate findings in these two strains, displaying important aspects of AD progression. TgCRND8 mice showed significantly decreased cerebral blood flow and glucose metabolism with unchanged cerebral blood volume (CBV) at 12 months-of-age whereas 5xFAD mice showed unaltered glucose metabolism with significant increase in CBV at 12 months-of-age and a biphasic pattern of early hypoperfusion followed by a rebound to normal cerebral blood flow in late disease. Finally, immunoblotting assays suggested that VEGF dependent vascular tone change may restore normoperfusion and increase CBV in 5xFAD.
登录
查看更多内容
影响因子：
9.3
作者：
Ryu JK;McLarnon JG
通讯作者：
McLarnon JG
影响因子：
16.2
作者：
Cortes-Canteli, Marta;Paul, Justin;Norris, Erin H.;Bronstein, Robert;Ahn, Hyung Jin;Zamolodchikov, Daria;Bhuvanendran, Shivaprasad;Fenz, Katherine M.;Strickland, Sidney
通讯作者：
Strickland, Sidney
影响因子：
5.3
作者：
Ben Haim L;Carrillo-de Sauvage MA;Ceyzériat K;Escartin C
通讯作者：
Escartin C
影响因子：
2.1
作者：
Chao LL;Buckley ST;Kornak J;Schuff N;Madison C;Yaffe K;Miller BL;Kramer JH;Weiner MW
通讯作者：
Weiner MW
影响因子：
3.8
作者：
Hall AM;Roberson ED
通讯作者：
Roberson ED