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dc.contributor.author
Martino Adami, Pamela Victoria
dc.contributor.author
Nichtová, Zuzana
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Weaver, David B.
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Bartok, Adam
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Wisniewski, Thomas
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Jones, Drew R.
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Do Carmo, Sonia
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Castaño, Eduardo Miguel
dc.contributor.author
Cuello, Claudio A.
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Hajnóczky, György
dc.contributor.author
Morelli, Laura
dc.date.available
2020-02-05T20:04:20Z
dc.date.issued
2019-10
dc.identifier.citation
Martino Adami, Pamela Victoria; Nichtová, Zuzana; Weaver, David B.; Bartok, Adam; Wisniewski, Thomas; et al.; Perturbed mitochondria-ER contacts in live neurons that model the amyloid pathology of Alzheimer's disease; Company of Biologists; Journal of Cell Science; 132; 20; 10-2019
dc.identifier.issn
0021-9533
dc.identifier.uri
http://hdl.handle.net/11336/96782
dc.description.abstract
The use of fixed fibroblasts from familial and sporadic Alzheimer's disease patients has previously indicated an upregulation of mitochondria-ER contacts (MERCs) as a hallmark of Alzheimer's disease. Despite its potential significance, the relevance of these results is limited because they were not extended to live neurons. Here we performed a dynamic in vivo analysis of MERCs in hippocampal neurons from McGill-R-Thy1-APP transgenic rats, a model of Alzheimer's disease-like amyloid pathology. Live FRET imaging of neurons from transgenic rats revealed perturbed 'lipid-MERCs' (gap width <10 nm), while 'Ca2+-MERCs' (10-20 nm gap width) were unchanged. In situ TEM showed no significant differences in the lipid- MERCs:totalMERCs or lipid-MERCs:mitochondria ratios; however, the average length of lipid-MERCs was significantly decreased in neurons from transgenic rats as compared to controls. In accordance with FRET results, untargeted lipidomics showed significant decreases in levels of 12 lipids and bioenergetic analysis revealed respiratory dysfunction of mitochondria from transgenic rats. Thus, our results reveal changes in MERC structures coupled with impaired mitochondrial functions in Alzheimer's disease-related neurons. This article has an associated First Person interview with the first author of the paper.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Company of Biologists
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
ALZHEIMER
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AMYLOID β/βCTF
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FRET
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MERC
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MITOCHONDRIAL LIPIDS
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PRIMARY NEURONAL CULTURES
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TRANSGENIC RATS
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Bioquímica y Biología Molecular
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Perturbed mitochondria-ER contacts in live neurons that model the amyloid pathology of Alzheimer's disease
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-12-11T20:12:53Z
dc.journal.volume
132
dc.journal.number
20
dc.journal.pais
Reino Unido
dc.journal.ciudad
Cambridge
dc.description.fil
Fil: Martino Adami, Pamela Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universitat zu Köln; Alemania
dc.description.fil
Fil: Nichtová, Zuzana. Thomas Jefferson University; Estados Unidos
dc.description.fil
Fil: Weaver, David B.. Thomas Jefferson University; Estados Unidos
dc.description.fil
Fil: Bartok, Adam. Thomas Jefferson University; Estados Unidos
dc.description.fil
Fil: Wisniewski, Thomas. University of New York; Estados Unidos
dc.description.fil
Fil: Jones, Drew R.. University of New York; Estados Unidos
dc.description.fil
Fil: Do Carmo, Sonia. Mcgill University; Canadá
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Fil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
dc.description.fil
Fil: Cuello, Claudio A.. Mcgill University; Canadá
dc.description.fil
Fil: Hajnóczky, György. Thomas Jefferson University; Estados Unidos
dc.description.fil
Fil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
dc.journal.title
Journal of Cell Science
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1242/jcs.229906
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://jcs.biologists.org/content/132/20/jcs229906
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