APP depletion alters selective pre- and post-synaptic proteins

The normal role of Alzheimer's disease (AD)-linked amyloid precursor protein (APP) in the brain remains incompletely understood. Previous studies have reported that lack of APP has detrimental effects on spines and electrophysiological parameters. APP has been described to be important in synap...

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Detalhes bibliográficos
Autores: Martinsson, lsak, Capetillo González de Zárate, Estíbaliz, Faideau, Mathilde, Willén, Katarina, Esteras, Noemi, Frykman, Susanne, Tjernberg, Lars O., Gouras, Gunnar K.
Tipo de documento: artigo
Data de publicação:2019
País:España
Recursos:Universidad del País Vasco
Repositório:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/32893
Acesso em linha:http://hdl.handle.net/10810/32893
Access Level:Acceso aberto
Palavra-chave:amyloid precursor protein
amyloid
synapse
alzheimer's disease
ampa receptors
alzheimers-disease
neurite outgrowth
spine density
beta
mice
plasticity
synapses
deficits
neurons
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repository_id_str
spelling APP depletion alters selective pre- and post-synaptic proteinsMartinsson, lsakCapetillo González de Zárate, EstíbalizFaideau, MathildeWillén, KatarinaEsteras, NoemiFrykman, SusanneTjernberg, Lars O.Gouras, Gunnar K.amyloid precursor proteinamyloidsynapsealzheimer's diseaseampa receptorsamyloid precursor proteinalzheimers-diseaseneurite outgrowthspine densitybetamiceplasticitysynapsesdeficitsneuronsThe normal role of Alzheimer's disease (AD)-linked amyloid precursor protein (APP) in the brain remains incompletely understood. Previous studies have reported that lack of APP has detrimental effects on spines and electrophysiological parameters. APP has been described to be important in synaptic pruning during development. The effect of APP knockout on mature synapses is complicated by this role in development. We previously reported on differential changes in synaptic proteins and receptors in APP mutant AD transgenic compared to wild-type neurons, which revealed selective decreases in levels of pre- and post-synaptic proteins, including of surface glutamate receptors. In the present study, we undertook a similar analysis of synaptic composition but now in APP knockout compared to wild-type mouse neurons. Here we demonstrate alterations in levels of selective pre- and post-synaptic proteins and receptors in APP knockout compared to wild-type mouse primary neurons in culture and brains of mice in youth and adulthood. Remarkably, we demonstrate selective increases in levels of synaptic proteins, such as GluA1, in neurons with APP knockout and with RNAi knockdown, which tended to be opposite to the reductions seen in AD transgenic APP mutant compared to wild-type neurons. These data reinforce that APP is important for the normal composition of synapses.We acknowledge the support of Prof. Bengt Winblad and Swedish Brain Power, Hjarnfonden, the Swedish Research Council grant 2015-02656 and NIH grant AG28174. We also thank Bodil Israelsson, Fangmin Yu, Sofie Bergstrand and Carolin Strobl for their technical assistance.Elsevier201920192019info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/32893reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoIngléshttps://www.sciencedirect.com/science/article/pii/S1044743118303609?via%3Dihubinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/3.0/es/© 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/)Atribución 3.0 Españaoai:addi.ehu.eus:10810/328932026-06-18T09:23:17Z
dc.title.none.fl_str_mv APP depletion alters selective pre- and post-synaptic proteins
title APP depletion alters selective pre- and post-synaptic proteins
spellingShingle APP depletion alters selective pre- and post-synaptic proteins
Martinsson, lsak
amyloid precursor protein
amyloid
synapse
alzheimer's disease
ampa receptors
amyloid precursor protein
alzheimers-disease
neurite outgrowth
spine density
beta
mice
plasticity
synapses
deficits
neurons
title_short APP depletion alters selective pre- and post-synaptic proteins
title_full APP depletion alters selective pre- and post-synaptic proteins
title_fullStr APP depletion alters selective pre- and post-synaptic proteins
title_full_unstemmed APP depletion alters selective pre- and post-synaptic proteins
title_sort APP depletion alters selective pre- and post-synaptic proteins
dc.creator.none.fl_str_mv Martinsson, lsak
Capetillo González de Zárate, Estíbaliz
Faideau, Mathilde
Willén, Katarina
Esteras, Noemi
Frykman, Susanne
Tjernberg, Lars O.
Gouras, Gunnar K.
author Martinsson, lsak
author_facet Martinsson, lsak
Capetillo González de Zárate, Estíbaliz
Faideau, Mathilde
Willén, Katarina
Esteras, Noemi
Frykman, Susanne
Tjernberg, Lars O.
Gouras, Gunnar K.
author_role author
author2 Capetillo González de Zárate, Estíbaliz
Faideau, Mathilde
Willén, Katarina
Esteras, Noemi
Frykman, Susanne
Tjernberg, Lars O.
Gouras, Gunnar K.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv amyloid precursor protein
amyloid
synapse
alzheimer's disease
ampa receptors
amyloid precursor protein
alzheimers-disease
neurite outgrowth
spine density
beta
mice
plasticity
synapses
deficits
neurons
topic amyloid precursor protein
amyloid
synapse
alzheimer's disease
ampa receptors
amyloid precursor protein
alzheimers-disease
neurite outgrowth
spine density
beta
mice
plasticity
synapses
deficits
neurons
description The normal role of Alzheimer's disease (AD)-linked amyloid precursor protein (APP) in the brain remains incompletely understood. Previous studies have reported that lack of APP has detrimental effects on spines and electrophysiological parameters. APP has been described to be important in synaptic pruning during development. The effect of APP knockout on mature synapses is complicated by this role in development. We previously reported on differential changes in synaptic proteins and receptors in APP mutant AD transgenic compared to wild-type neurons, which revealed selective decreases in levels of pre- and post-synaptic proteins, including of surface glutamate receptors. In the present study, we undertook a similar analysis of synaptic composition but now in APP knockout compared to wild-type mouse neurons. Here we demonstrate alterations in levels of selective pre- and post-synaptic proteins and receptors in APP knockout compared to wild-type mouse primary neurons in culture and brains of mice in youth and adulthood. Remarkably, we demonstrate selective increases in levels of synaptic proteins, such as GluA1, in neurons with APP knockout and with RNAi knockdown, which tended to be opposite to the reductions seen in AD transgenic APP mutant compared to wild-type neurons. These data reinforce that APP is important for the normal composition of synapses.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/32893
url http://hdl.handle.net/10810/32893
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://www.sciencedirect.com/science/article/pii/S1044743118303609?via%3Dihub
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es/
Atribución 3.0 España
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/3.0/es/
Atribución 3.0 España
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:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301603

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