Pathological tau and reactive astrogliosis are associated with distinct functional deficits in a mouse model of tauopathy.
Pathological tau and reactive astrogliosis are associated with distinct functional deficits in a mouse model of tauopathy.
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DOI：
10.1016/j.neurobiolaging.2021.09.006
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发表时间：
2022-01
影响因子：
4.2
通讯作者：
Lasagna-Reeves CA
中科院分区：
文献类型：
--
作者：
Patel H;Martinez P;Perkins A;Taylor X;Jury N;McKinzie D;Lasagna-Reeves CA
tau 蛋白的病理性聚集和神经炎症变化标志着阿尔茨海默病和相关 tau 蛋白病的临床病程。为了了解这些病理特征和功能缺陷之间的相关性，我们评估了 PS19 小鼠模型（一种广泛使用的 tau 蛋白病模型）的行为和生理缺陷。 9个月时，PS19小鼠表现出特征性的过度活跃行为、运动强度下降和生理状况恶化，表现为体温降低、体重减轻和虚弱程度增加。这些缺陷与不同病理特征的相关性表明，以可溶性 p-tau 物种为特征的病理性 tau 物种和 tau 种子生物活性与握力和热调节受损相关。另一方面，星形胶质细胞反应性与 PS19 小鼠的过度活跃行为呈正相关。这些结果表明，多种可溶性病理性 tau 物种可能导致不同的症状，并且神经炎症可能独立于 tau 病理学而导致功能缺陷。这些观察结果增强了治疗神经退行性tau蛋白病的多靶点方法的必要性。
Pathological aggregation of tau and neuroinflammatory changes mark the clinical course of Alzheimer’s disease and related tauopathies. To understand the correlation between these pathological hallmarks and functional deficits, we assessed behavioral and physiological deficits in the PS19 mouse model, a broadly utilized model of tauopathy. At 9 months, PS19 mice have characteristic hyperactive behavior, a decline in motor strength, and deterioration in physiological conditions marked by lower body temperature, reduced body weight, and an increase in measures of frailty. Correlation of these deficits with different pathological hallmarks revealed that pathological tau species, characterized by soluble p-tau species, and tau seeding bioactivity correlated with impairment in grip strength and thermal regulation. On the other hand, astrocyte reactivity showed a positive correlation with the hyperactive behavior of the PS19 mice. These results suggest that a diverse spectrum of soluble pathological tau species could be responsible for different symptoms and that neuroinflammation could contribute to functional deficits independently from tau pathology. These observations enhance the necessity of a multi-targeted approach for the treatment of neurodegenerative tauopathies.
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影响因子：
4.3
作者：
DeVos SL;Corjuc BT;Oakley DH;Nobuhara CK;Bannon RN;Chase A;Commins C;Gonzalez JA;Dooley PM;Frosch MP;Hyman BT
通讯作者：
Hyman BT
影响因子：
5.3
作者：
Castillo-Carranza, Diana L.;Sengupta, Urmi;Kayed, Rakez
通讯作者：
Kayed, Rakez
影响因子：
14.5
作者：
de Gerando, Anastasie Mate;d'Orange, Marie;Cambon, Karine
通讯作者：
Cambon, Karine
影响因子：
8.6
作者：
Henkel, K;Karitzky, J;Landwehrmeyer, GB
通讯作者：
Landwehrmeyer, GB
DOI：
10.1080/10409238.2016.1226251
发表时间：
2016
影响因子：
6.5
作者：
Gerson JE;Mudher A;Kayed R
通讯作者：
Kayed R