Stress acts cumulatively to precipitate Alzheimer’s disease-like tau pathology and cognitive deficits
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/18640 |
Resumo: | 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. |
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Stress acts cumulatively to precipitate Alzheimer’s disease-like tau pathology and cognitive deficitsScience & TechnologyStressful 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.Marie Curie Training FellowshipsEU CRESCENDO Consortium contract FP6-018652University College, London.Max Planck Society and European Union (EU) German-Portuguese Luso-Alemas Program and the EU CRESCENDO Consortium (Contract FP6-018652).German-Portuguese Luso-Alemas ProgramSociety for NeuroscienceUniversidade do MinhoSotiropoulos, I.Catania, C.Pinto, Lucilia G.Silva, RuiPollerberg, G. ElizabethTakashima, AkihikoSousa, NunoAlmeida, O. F. X.2011-052011-05-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/18640eng1529-240110.1523/JNEUROSCI.0730-11.201121613497http://www.jneurosci.org/content/31/21/7840.longinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T11:59:46Zoai:repositorium.sdum.uminho.pt:1822/18640Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:49:35.073918Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Stress acts cumulatively to precipitate Alzheimer’s disease-like tau pathology and cognitive deficits |
title |
Stress acts cumulatively to precipitate Alzheimer’s disease-like tau pathology and cognitive deficits |
spellingShingle |
Stress acts cumulatively to precipitate Alzheimer’s disease-like tau pathology and cognitive deficits Sotiropoulos, I. Science & Technology |
title_short |
Stress acts cumulatively to precipitate Alzheimer’s disease-like tau pathology and cognitive deficits |
title_full |
Stress acts cumulatively to precipitate Alzheimer’s disease-like tau pathology and cognitive deficits |
title_fullStr |
Stress acts cumulatively to precipitate Alzheimer’s disease-like tau pathology and cognitive deficits |
title_full_unstemmed |
Stress acts cumulatively to precipitate Alzheimer’s disease-like tau pathology and cognitive deficits |
title_sort |
Stress acts cumulatively to precipitate Alzheimer’s disease-like tau pathology and cognitive deficits |
author |
Sotiropoulos, I. |
author_facet |
Sotiropoulos, I. Catania, C. Pinto, Lucilia G. Silva, Rui Pollerberg, G. Elizabeth Takashima, Akihiko Sousa, Nuno Almeida, O. F. X. |
author_role |
author |
author2 |
Catania, C. Pinto, Lucilia G. Silva, Rui Pollerberg, G. Elizabeth Takashima, Akihiko Sousa, Nuno Almeida, O. F. X. |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Sotiropoulos, I. Catania, C. Pinto, Lucilia G. Silva, Rui Pollerberg, G. Elizabeth Takashima, Akihiko Sousa, Nuno Almeida, O. F. X. |
dc.subject.por.fl_str_mv |
Science & Technology |
topic |
Science & Technology |
description |
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. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011-05 2011-05-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/18640 |
url |
http://hdl.handle.net/1822/18640 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1529-2401 10.1523/JNEUROSCI.0730-11.2011 21613497 http://www.jneurosci.org/content/31/21/7840.long |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Society for Neuroscience |
publisher.none.fl_str_mv |
Society for Neuroscience |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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