2016
DOI: 10.1073/pnas.1600953113
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Abstract: 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 … Show more

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Cited by 121 publications
(118 citation statements)
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“…Clinical studies suggest that stressful life events and high GC levels are risk factors for AD (Johansson et al , ; Machado et al , ); and animal studies demonstrate that prolonged exposure to environmental stress and/or elevated GC levels trigger Tau accumulation (Lopes et al , ,c; Vyas et al , ). Based on our findings identifying the Rab35/ESCRT pathway as a critical regulator of Tau degradation, we next examined whether GC treatment altered the levels of Rab35 or ESCRT pathway proteins.…”
Section: Resultsmentioning
confidence: 99%
“…Clinical studies suggest that stressful life events and high GC levels are risk factors for AD (Johansson et al , ; Machado et al , ); and animal studies demonstrate that prolonged exposure to environmental stress and/or elevated GC levels trigger Tau accumulation (Lopes et al , ,c; Vyas et al , ). Based on our findings identifying the Rab35/ESCRT pathway as a critical regulator of Tau degradation, we next examined whether GC treatment altered the levels of Rab35 or ESCRT pathway proteins.…”
Section: Resultsmentioning
confidence: 99%
“…The fact that mice with genetic invalidation of tau survive in adulthood somewhat normally indicates that hyperphosphorylation of tau provides a gain-of-function more deleterious than the loss-of-function. For instance, knockout of tau blocks the behavioral, morphological and biochemical responses to chronic glucocorticoid administration or chronic stress, suggesting that hyperphosphorylated tau may deviate neuroplasticity from adaptation to maladaptation14.…”
Section: Discussionmentioning
confidence: 99%
“…Stress and glucocorticoids increase tau phosphorylation in dendrites and synapses commensurate to the intensity of stimuli1314. It is hypothesized that stress and glucocorticoid-induced tau phosphorylation is transient or reversible.…”
Section: Discussionmentioning
confidence: 99%
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“…Studies must control for alcohol and substance misuse,34 performance enhancing drugs,35 mood and stress disorders36 among known problems. The potential neurotoxic effects of performance-enhancing drugs, including those permitted by World Anti-Doping Agency such as tramadol, are the ‘elephant in the room’ which has been seldom discussed in this debate.…”
Section: A Little Less Conversation a Little More Science Pleasementioning
confidence: 99%