期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 26, 页码 E3755-E3763出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1600953113
关键词
Tau; stress; hippocampus; depression; memory deficits
资金
- Portuguese Foundation for Science & Technology (FCT) [PTDC/SAU-NMC/113934/2009]
- European Union FP7 Project SwitchBox
- Portuguese North Regional Operational Program (ON.2-O Novo Norte) under the National Strategic Reference Framework (QREN) through the European Regional Development Fund (FEDER)
- Education and Lifelong Learning, Supporting Postdoctoral Researchers and Large Scale Cooperative Project
- European Social Fund
- Greek General Secretariat for Research and Technology
- University of Minho MD/PhD Program - FCT [PD/BD/105938/2014]
Exposure to chronic stress is frequently accompanied by cognitive and affective disorders in association with neurostructural adaptations. Chronic stress was previously shown to trigger Alzheimer's-like neuropathology, which is characterized by Tau hyper-phosphorylation and missorting into dendritic spines followed by memory deficits. Here, we demonstrate that stress-driven hippocampal deficits in wild-type mice are accompanied by synaptic missorting of Tau and enhanced Fyn/GluN2B-driven synaptic signaling. In contrast, mice lacking Tau [Tau knockout (Tau-KO) mice] do not exhibit stress-induced pathological behaviors and atrophy of hippocampal dendrites or deficits of hippocampal connectivity. These findings implicate Tau as an essential mediator of the adverse effects of stress on brain structure and function.
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