Striatal fibrinogen extravasation and vascular degeneration correlate with motor dysfunction in an aging mouse model of Alzheimer's disease.
Striatal fibrinogen extravasation and vascular degeneration correlate with motor dysfunction in an aging mouse model of Alzheimer's disease.
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DOI：
10.3389/fnagi.2023.1064178
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发表时间：
2023
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
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前言：阿尔茨海默病(AD)患者表现出运动功能障碍的迹象，包括步态、运动和平衡障碍。运动功能的改变通常先于AD的其他症状，并与严重程度和死亡率的增加相关。尽管AD患者经常出现运动功能障碍，但人们对这种行为改变的机制知之甚少。方法和结果：在本研究中，我们在AD小鼠模型(Tg6799)中研究了脑血管损伤和运动功能障碍之间的关系。我们发现AD小鼠大脑皮质和纹状体中渗出的纤维蛋白原沉积随年龄增加。有趣的是，与7个月大的AD小鼠相比，15个月大的小鼠纹状体内脑血管密度显著降低。我们还发现老年AD小鼠纹状体有明显的脱髓鞘和轴突损伤。我们分析了两个年龄段的AD小鼠的纹状体相关运动功能和焦虑水平，发现老年AD小鼠表现出明显的运动功能障碍，而年轻AD小鼠则没有。讨论：我们的发现表明，在AD小鼠模型中，纤维蛋白原渗出、纹状体脑血管损伤和运动功能障碍之间存在诱人的相关性，提示AD运动功能障碍的可能机制。
Introduction: Alzheimer’s Disease (AD) patients exhibit signs of motor dysfunction, including gait, locomotion, and balance deficits. Changes in motor function often precede other symptoms of AD as well as correlate with increased severity and mortality. Despite the frequent occurrence of motor dysfunction in AD patients, little is known about the mechanisms by which this behavior is altered. Methods and Results: In the present study, we investigated the relationship between cerebrovascular impairment and motor dysfunction in a mouse model of AD (Tg6799). We found an age-dependent increase of extravasated fibrinogen deposits in the cortex and striatum of AD mice. Interestingly, there was significantly decreased cerebrovascular density in the striatum of the 15-month-old as compared to 7-month-old AD mice. We also found significant demyelination and axonal damage in the striatum of aged AD mice. We analyzed striatum-related motor function and anxiety levels of AD mice at both ages and found that aged AD mice exhibited significant impairment of motor function but not in the younger AD mice. Discussion: Our finding suggests an enticing correlation between extravasated fibrinogen, cerebrovascular damage of the striatum, and motor dysfunction in an AD mouse model, suggesting a possible mechanism underlying motor dysfunction in AD.
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小鼠皮质-基底节-丘脑网络。
影响因子：
64.8
作者：
Foster NN;Barry J;Korobkova L;Garcia L;Gao L;Becerra M;Sherafat Y;Peng B;Li X;Choi JH;Gou L;Zingg B;Azam S;Lo D;Khanjani N;Zhang B;Stanis J;Bowman I;Cotter K;Cao C;Yamashita S;Tugangui A;Li A;Jiang T;Jia X;Feng Z;Aquino S;Mun HS;Zhu M;Santarelli A;Benavidez NL;Song M;Dan G;Fayzullina M;Ustrell S;Boesen T;Johnson DL;Xu H;Bienkowski MS;Yang XW;Gong H;Levine MS;Wickersham I;Luo Q;Hahn JD;Lim BK;Zhang LI;Cepeda C;Hintiryan H;Dong HW
通讯作者：
Dong HW
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：
16.6
作者：
通讯作者：
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影响因子：
2.9
作者：
Bunner KD;Rebec GV
通讯作者：
Rebec GV
DOI：
10.1073/pnas.1921327117
发表时间：
2020-06-23
影响因子：
11.1
作者：
Cajamarca, Steven A.;Norris, Erin H.;Ahn, Hyung Jin
通讯作者：
Ahn, Hyung Jin