Please use this identifier to cite or link to this item:

TitleStress acts cumulatively to precipitate Alzheimer’s disease-like tau pathology and cognitive deficits
Author(s)Sotiropoulos, I.
Catania, C.
Pinto, Lucilia G.
Silva, Rui
Pollerberg, G. Elizabeth
Takashima, Akihiko
Sousa, Nuno
Almeida, O. F. X.
Issue dateMay-2011
PublisherSociety for Neuroscience
JournalJournal of Neuroscience
Abstract(s)Stressful life experiences are likely tiological factors in sporadic forms of Alzheimer’s disease (AD). Many AD patients hypersecrete glucocorticoids (GCs), and their GC levels correlate with the rate of cognitive impairment and extent of neuronal atrophy. Severity of cognitive deficits in AD correlates strongly with levels of perphosphorylated forms of the cytoskeletal protein TAU, an essential mediator of the actions of amyloid Beta (ABeta ), another molecule with a key pathogenic role in AD. Our objective was to investigate the sequential interrelationships between these various pathogenic elements, in particular with respect to the mechanisms through which stress might precipitate cognitive decline. We thus examined whether stress, through the mediation of GCs, influences TAU hyperphosphorylation, a critical and early event in the cascade of processes leading to AD pathology. Results from healthy, wild-type, middle-aged rats show that chronic stress and GC induce abnormal hyperphosphorylation of TAU in the hippocampus and prefrontal cortex (PFC), with contemporaneous impairments of hippocampus- and PFC-dependent behaviors. Exogenous GC potentiated the ability of centrally infused ABeta to induce hyperphosphorylation of TAU epitopes associated with AD and cytoplasmic accumulation of TAU, while previous exposure to stress aggravated the biochemical and behavioral effects of GC in ABeta-infused animals. Thus, lifetime stress/GC exposure may have a cumulative impact on the onset and progress of AD pathology, with TAU hyperphosphorylation serving to transduce the negative effects of stress and GC on cognition.
Publisher version
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

Files in This Item:
File Description SizeFormat 
Sotiropoulos I_Journal of Neuroscience 2011.pdfDocumento principal1,54 MBAdobe PDFView/Open

Partilhe no FacebookPartilhe no TwitterPartilhe no DeliciousPartilhe no LinkedInPartilhe no DiggAdicionar ao Google BookmarksPartilhe no MySpacePartilhe no Orkut
Exporte no formato BibTex mendeley Exporte no formato Endnote Adicione ao seu ORCID