Microtubule-associated protein tau is essential for long-term depression in the hippocampus
Autor(a) principal: | |
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Data de Publicação: | 2014 |
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/1822/28455 |
Resumo: | The microtubule-associated protein tau is a principal component of neurofibrillary tangles, and has been identified as a key molecule in Alzheimer's disease and other tauopathies. However, it is unknown how a protein that is primarily located in axons is involved in a disease that is believed to have a synaptic origin. To investigate a possible synaptic function of tau, we studied synaptic plasticity in the hippocampus and found a selective deficit in long-term depression (LTD) in tau knockout mice in vivo and in vitro, an effect that was replicated by RNAi knockdown of tau in vitro. We found that the induction of LTD is associated with the glycogen synthase kinase-3-mediated phosphorylation of tau. These observations demonstrate that tau has a critical physiological function in LTD. |
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Microtubule-associated protein tau is essential for long-term depression in the hippocampusAlzheimer's diseasehippocampussynaptic plasticitylong-term depressiontauScience & TechnologyThe microtubule-associated protein tau is a principal component of neurofibrillary tangles, and has been identified as a key molecule in Alzheimer's disease and other tauopathies. However, it is unknown how a protein that is primarily located in axons is involved in a disease that is believed to have a synaptic origin. To investigate a possible synaptic function of tau, we studied synaptic plasticity in the hippocampus and found a selective deficit in long-term depression (LTD) in tau knockout mice in vivo and in vitro, an effect that was replicated by RNAi knockdown of tau in vitro. We found that the induction of LTD is associated with the glycogen synthase kinase-3-mediated phosphorylation of tau. These observations demonstrate that tau has a critical physiological function in LTD.A.T. was supported by the research funding for longevity sciences (23-39) from National Center for Geriatrics and Gerontology, and the Strategic Research Programme for Brain Science ('Integrated Research on Neuropsychiatric Disorders') and Grant in Aid for Scientific Research on Innovative Areas ('Brain Environment') from the Ministry of Education, Science, Sports and Culture of Japan. K.C., D.J.W. and G.L.C. were supported by UK Wellcome Trust-MRC Neurodegenerative Disease Initiative Programme. K.C. was supported by the Korea-UK Alzheimer's Disease Research Consortium programme from the Ministry of Health and Welfare (Korea). G.L.C. was supported by the WCU Programme (Korea). I.S. was supported by the British Council. The collaboration between K.C. and A.T. was supported by a Sasakawa Foundation grant awarded to K.C. K.C. was supported by the Wolfson Research Merit Award and the Royal Society, London.Royal SocietyUniversidade do MinhoKimura, TetsuyaWhitcomb, Daniel J.Jo, JihoonRegan, PhilipPiers, ThomasHeo, SeonghooBrown, ChristopherHashikawa, TsutomuMurayama, MiyukiSeok, HeonSotiropoulos, I.Kim, EunjoonCollingridge, Graham L.Takashima, AkihikoCho, Kwangwook20142014-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/28455eng0962-843610.1098/rstb.2013.014424298146http://rstb.royalsocietypublishing.org/info: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:RCAAP2023-07-21T12:16:09Zoai:repositorium.sdum.uminho.pt:1822/28455Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:08:40.355025Repositório 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 |
Microtubule-associated protein tau is essential for long-term depression in the hippocampus |
title |
Microtubule-associated protein tau is essential for long-term depression in the hippocampus |
spellingShingle |
Microtubule-associated protein tau is essential for long-term depression in the hippocampus Kimura, Tetsuya Alzheimer's disease hippocampus synaptic plasticity long-term depression tau Science & Technology |
title_short |
Microtubule-associated protein tau is essential for long-term depression in the hippocampus |
title_full |
Microtubule-associated protein tau is essential for long-term depression in the hippocampus |
title_fullStr |
Microtubule-associated protein tau is essential for long-term depression in the hippocampus |
title_full_unstemmed |
Microtubule-associated protein tau is essential for long-term depression in the hippocampus |
title_sort |
Microtubule-associated protein tau is essential for long-term depression in the hippocampus |
author |
Kimura, Tetsuya |
author_facet |
Kimura, Tetsuya Whitcomb, Daniel J. Jo, Jihoon Regan, Philip Piers, Thomas Heo, Seonghoo Brown, Christopher Hashikawa, Tsutomu Murayama, Miyuki Seok, Heon Sotiropoulos, I. Kim, Eunjoon Collingridge, Graham L. Takashima, Akihiko Cho, Kwangwook |
author_role |
author |
author2 |
Whitcomb, Daniel J. Jo, Jihoon Regan, Philip Piers, Thomas Heo, Seonghoo Brown, Christopher Hashikawa, Tsutomu Murayama, Miyuki Seok, Heon Sotiropoulos, I. Kim, Eunjoon Collingridge, Graham L. Takashima, Akihiko Cho, Kwangwook |
author2_role |
author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Kimura, Tetsuya Whitcomb, Daniel J. Jo, Jihoon Regan, Philip Piers, Thomas Heo, Seonghoo Brown, Christopher Hashikawa, Tsutomu Murayama, Miyuki Seok, Heon Sotiropoulos, I. Kim, Eunjoon Collingridge, Graham L. Takashima, Akihiko Cho, Kwangwook |
dc.subject.por.fl_str_mv |
Alzheimer's disease hippocampus synaptic plasticity long-term depression tau Science & Technology |
topic |
Alzheimer's disease hippocampus synaptic plasticity long-term depression tau Science & Technology |
description |
The microtubule-associated protein tau is a principal component of neurofibrillary tangles, and has been identified as a key molecule in Alzheimer's disease and other tauopathies. However, it is unknown how a protein that is primarily located in axons is involved in a disease that is believed to have a synaptic origin. To investigate a possible synaptic function of tau, we studied synaptic plasticity in the hippocampus and found a selective deficit in long-term depression (LTD) in tau knockout mice in vivo and in vitro, an effect that was replicated by RNAi knockdown of tau in vitro. We found that the induction of LTD is associated with the glycogen synthase kinase-3-mediated phosphorylation of tau. These observations demonstrate that tau has a critical physiological function in LTD. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014 2014-01-01T00:00:00Z |
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/1822/28455 |
url |
http://hdl.handle.net/1822/28455 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0962-8436 10.1098/rstb.2013.0144 24298146 http://rstb.royalsocietypublishing.org/ |
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 |
Royal Society |
publisher.none.fl_str_mv |
Royal Society |
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 |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799132509230858240 |