Tau protein is essential for stress-induced brain pathology.
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 hyperphosphorylation 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.
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, 4710-057 Braga/Guimarães, Portugal;
Sofia
S
Lopes
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, 4710-057 Braga/Guimarães, Portugal;
João
J
Vaz-Silva
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, 4710-057 Braga/Guimarães, Portugal;
Vitor
V
Pinto
Department of Pharmacology, Medical School of Athens, 11527 Goudi, Greece;
Christina
C
Dalla
Department of Pharmacology, Medical School of Athens, 11527 Goudi, Greece;
Nikolaos
N
Kokras
Max Planck Institute of Psychiatry, 80804 Munich, Germany.
Benedikt
B
Bedenk
Max Planck Institute of Psychiatry, 80804 Munich, Germany.
Natalie
N
Mack
Max Planck Institute of Psychiatry, 80804 Munich, Germany.
Michael
M
Czisch
Max Planck Institute of Psychiatry, 80804 Munich, Germany.
Osborne F X
OF
Almeida
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, 4710-057 Braga/Guimarães, Portugal;
Nuno
N
Sousa
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, 4710-057 Braga/Guimarães, Portugal; ioannis@ecsaude.uminho.pt.
Ioannis
I
Sotiropoulos
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D049229:Dendritic Spines / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D013312:Stress, Physiological; D013569:Synapses / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C491468:Fyb protein, mouse; D016875:tau Proteins
Tau; depression; hippocampus; memory deficits; stress