Excess synaptojanin 1 contributes to place cell dysfunction and memory deficits in the aging hippocampus in three types of Alzheimer's disease
Autor(a) principal: | |
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Data de Publicação: | 2018 |
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/1822/57896 |
Resumo: | The phosphoinositide phosphatase synaptojanin 1 (SYNJ1) is a key regulator of synaptic function. We first tested whether SYNJ1 contributes to phenotypic variations in familial Alzheimer's disease (FAD) and show that SYNJ1 polymorphisms are associated with age of onset in both early- and late-onset human FAD cohorts. We then interrogated whether SYNJ1 levels could directly affect memory. We show that increased SYNJ1 levels in autopsy brains from adults with Down syndrome (DS/AD) are inversely correlated with synaptophysin levels, a direct readout of synaptic integrity. We further report age-dependent cognitive decline in a mouse model overexpressing murine Synj1 to the levels observed in human sporadic AD, triggered through hippocampal hyperexcitability and defects in the spatial reproducibility of place fields. Taken together, our findings suggest that SYNJ1 contributes to memory deficits in the aging hippocampus in all forms of AD. |
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Excess synaptojanin 1 contributes to place cell dysfunction and memory deficits in the aging hippocampus in three types of Alzheimer's diseasehyperexcitabilityin vivo electrophysiologyLong-term memoryneurodegenerative disorderssingle nucleotide polymorphismssynaptic dysfunctionSYNJ1Ciências Médicas::Medicina BásicaScience & TechnologyThe phosphoinositide phosphatase synaptojanin 1 (SYNJ1) is a key regulator of synaptic function. We first tested whether SYNJ1 contributes to phenotypic variations in familial Alzheimer's disease (FAD) and show that SYNJ1 polymorphisms are associated with age of onset in both early- and late-onset human FAD cohorts. We then interrogated whether SYNJ1 levels could directly affect memory. We show that increased SYNJ1 levels in autopsy brains from adults with Down syndrome (DS/AD) are inversely correlated with synaptophysin levels, a direct readout of synaptic integrity. We further report age-dependent cognitive decline in a mouse model overexpressing murine Synj1 to the levels observed in human sporadic AD, triggered through hippocampal hyperexcitability and defects in the spatial reproducibility of place fields. Taken together, our findings suggest that SYNJ1 contributes to memory deficits in the aging hippocampus in all forms of AD.Fundação para a Ciência e Tecnologia (PD/BD/105915/2014 to A.M.M.), the Philippe Chatrier Foundation (C.M.), the Lejeune Foundation (1149 to G.D.P.), the Alzheimer’s Association (2015-NIRG-341570 to S.A.H.), ANR Investissements d’Avenir (ANR-10-IAIHU-06 to M.-C.P.), and the NIH (R01AG050425 to S.A.H.; RO1HD064993 to E.H. and F.A.S.; and RO1HD065160, P50AG16573, and U01AG051412 to I.T.L.). Data collection on Caribbean Hispanic families with at least one G206A founder mutation in the PSEN1 gene was supported by the BrightFocus Foundation (A2015633S) and NIH/National Institute on Aging (NIA) (R56 AG051876-01A1) to J.H.L. Data collection for the EFIGA project was supported by the Genetic Studies of Alzheimer’s Disease in Caribbean Hispanics (EFIGA), funded by the NIH/NIA (5R37AG015473, RF1AG015473, and R56AG051876). We acknowledge the EFIGA study participants and the EFIGA research and support staff for their contributions to this studyinfo:eu-repo/semantics/publishedVersionElsevierUniversidade do MinhoMiranda, André Miguel LopesHerman, MathieuCheng, RongNahmani, EdenBarrett, GeoffreyMicevska, ElizabetaFontaine, GaellePotier, Marie-ClaudeHead, ElizabethSchmitt, Frederick A.Lott, Ira T.Jiménez-Velázquez, Ivonne Z.Antonarakis, Stylianos E.Di Paolo, GilbertLee, Joseph H.Hussaini, S. AbidMarquer, Catherine2018-06-052018-06-05T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/57896eng130. Miranda, A. M., Herman, M., Cheng, R., Nahmani, E., Barrett, G., Micevska, E., . . . Marquer, C. (2018). Excess Synaptojanin 1 Contributes to Place Cell Dysfunction and Memory Deficits in the Aging Hippocampus in Three Types of Alzheimer's Disease. [Article]. Cell Reports, 23(10), 2967-2975. doi: 10.1016/j.celrep.2018.05.0112211-12472211-124710.1016/j.celrep.2018.05.01129874583https://www.cell.com/cell-reports/fulltext/S2211-1247(18)30744-7info: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:RCAAP2023-07-21T12:38:14Zoai:repositorium.sdum.uminho.pt:1822/57896Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:34:38.156638Repositório 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 |
Excess synaptojanin 1 contributes to place cell dysfunction and memory deficits in the aging hippocampus in three types of Alzheimer's disease |
title |
Excess synaptojanin 1 contributes to place cell dysfunction and memory deficits in the aging hippocampus in three types of Alzheimer's disease |
spellingShingle |
Excess synaptojanin 1 contributes to place cell dysfunction and memory deficits in the aging hippocampus in three types of Alzheimer's disease Miranda, André Miguel Lopes hyperexcitability in vivo electrophysiology Long-term memory neurodegenerative disorders single nucleotide polymorphisms synaptic dysfunction SYNJ1 Ciências Médicas::Medicina Básica Science & Technology |
title_short |
Excess synaptojanin 1 contributes to place cell dysfunction and memory deficits in the aging hippocampus in three types of Alzheimer's disease |
title_full |
Excess synaptojanin 1 contributes to place cell dysfunction and memory deficits in the aging hippocampus in three types of Alzheimer's disease |
title_fullStr |
Excess synaptojanin 1 contributes to place cell dysfunction and memory deficits in the aging hippocampus in three types of Alzheimer's disease |
title_full_unstemmed |
Excess synaptojanin 1 contributes to place cell dysfunction and memory deficits in the aging hippocampus in three types of Alzheimer's disease |
title_sort |
Excess synaptojanin 1 contributes to place cell dysfunction and memory deficits in the aging hippocampus in three types of Alzheimer's disease |
author |
Miranda, André Miguel Lopes |
author_facet |
Miranda, André Miguel Lopes Herman, Mathieu Cheng, Rong Nahmani, Eden Barrett, Geoffrey Micevska, Elizabeta Fontaine, Gaelle Potier, Marie-Claude Head, Elizabeth Schmitt, Frederick A. Lott, Ira T. Jiménez-Velázquez, Ivonne Z. Antonarakis, Stylianos E. Di Paolo, Gilbert Lee, Joseph H. Hussaini, S. Abid Marquer, Catherine |
author_role |
author |
author2 |
Herman, Mathieu Cheng, Rong Nahmani, Eden Barrett, Geoffrey Micevska, Elizabeta Fontaine, Gaelle Potier, Marie-Claude Head, Elizabeth Schmitt, Frederick A. Lott, Ira T. Jiménez-Velázquez, Ivonne Z. Antonarakis, Stylianos E. Di Paolo, Gilbert Lee, Joseph H. Hussaini, S. Abid Marquer, Catherine |
author2_role |
author author 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 |
Miranda, André Miguel Lopes Herman, Mathieu Cheng, Rong Nahmani, Eden Barrett, Geoffrey Micevska, Elizabeta Fontaine, Gaelle Potier, Marie-Claude Head, Elizabeth Schmitt, Frederick A. Lott, Ira T. Jiménez-Velázquez, Ivonne Z. Antonarakis, Stylianos E. Di Paolo, Gilbert Lee, Joseph H. Hussaini, S. Abid Marquer, Catherine |
dc.subject.por.fl_str_mv |
hyperexcitability in vivo electrophysiology Long-term memory neurodegenerative disorders single nucleotide polymorphisms synaptic dysfunction SYNJ1 Ciências Médicas::Medicina Básica Science & Technology |
topic |
hyperexcitability in vivo electrophysiology Long-term memory neurodegenerative disorders single nucleotide polymorphisms synaptic dysfunction SYNJ1 Ciências Médicas::Medicina Básica Science & Technology |
description |
The phosphoinositide phosphatase synaptojanin 1 (SYNJ1) is a key regulator of synaptic function. We first tested whether SYNJ1 contributes to phenotypic variations in familial Alzheimer's disease (FAD) and show that SYNJ1 polymorphisms are associated with age of onset in both early- and late-onset human FAD cohorts. We then interrogated whether SYNJ1 levels could directly affect memory. We show that increased SYNJ1 levels in autopsy brains from adults with Down syndrome (DS/AD) are inversely correlated with synaptophysin levels, a direct readout of synaptic integrity. We further report age-dependent cognitive decline in a mouse model overexpressing murine Synj1 to the levels observed in human sporadic AD, triggered through hippocampal hyperexcitability and defects in the spatial reproducibility of place fields. Taken together, our findings suggest that SYNJ1 contributes to memory deficits in the aging hippocampus in all forms of AD. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-06-05 2018-06-05T00:00:00Z |
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/1822/57896 |
url |
http://hdl.handle.net/1822/57896 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
130. Miranda, A. M., Herman, M., Cheng, R., Nahmani, E., Barrett, G., Micevska, E., . . . Marquer, C. (2018). Excess Synaptojanin 1 Contributes to Place Cell Dysfunction and Memory Deficits in the Aging Hippocampus in Three Types of Alzheimer's Disease. [Article]. Cell Reports, 23(10), 2967-2975. doi: 10.1016/j.celrep.2018.05.011 2211-1247 2211-1247 10.1016/j.celrep.2018.05.011 29874583 https://www.cell.com/cell-reports/fulltext/S2211-1247(18)30744-7 |
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 |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
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 |
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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) |
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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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