GSK3β inhibition promotes synaptogenesis in Drosophila and mammalian neurons

The PI3K-dependent activation of AKT results in the inhibition of GSK3β in most signaling pathways. These kinases regulate multiple neuronal processes including the control of synapse number as shown for Drosophila and rodents. Alzheimer disease's patients exhibit high levels of circulating GSK...

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Detalhes bibliográficos
Autores: Cuesto, Germán, Jordán-Álvarez, Sheila, Enríquez-Barreto, Lilian, Ferrús, Alberto, Morales, Miguel, Acebes, Ángel
Formato: artículo
Fecha de publicación:2015
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:154813
Acesso em linha:https://ddd.uab.cat/record/154813
https://dx.doi.org/urn:doi:10.1371/journal.pone.0118475
Access Level:acceso abierto
Palavra-chave:Synapses
Neurons
Drosophila melanogaster
Phosphorylation
Neuronal dendrites
Cell signaling
Larvae
Serine
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spelling GSK3β inhibition promotes synaptogenesis in Drosophila and mammalian neuronsCuesto, GermánJordán-Álvarez, SheilaEnríquez-Barreto, LilianFerrús, AlbertoMorales, MiguelAcebes, ÁngelSynapsesNeuronsDrosophila melanogasterPhosphorylationNeuronal dendritesCell signalingLarvaeSerineThe PI3K-dependent activation of AKT results in the inhibition of GSK3β in most signaling pathways. These kinases regulate multiple neuronal processes including the control of synapse number as shown for Drosophila and rodents. Alzheimer disease's patients exhibit high levels of circulating GSK3β and, consequently, pharmacological strategies based on GSK3β antagonists have been designed. The approach, however, has yielded inconclusive results so far. Here, we carried out a comparative study in Drosophila and rats addressing the role of GSK3β in synaptogenesis. In flies, the genetic inhibition of the shaggy-encoded GSK3β increases the number of synapses, while its upregulation leads to synapse loss. Likewise, in three weeks cultured rat hippocampal neurons, the pharmacological inhibition of GSK3β increases synapse density and Synapsin expression. However, experiments on younger cultures (12 days) yielded an opposite effect, a reduction of synapse density. This unexpected finding seems to unveil an age- and dosage-dependent differential response of mammalian neurons to the stimulation/inhibition of GSK3β, a feature that must be considered in the context of human adult neurogenesis and pharmacological treatments for Alzheimer's disease based on GSK3β antagonists. 22015-01-0120152015-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/154813https://dx.doi.org/urn:doi:10.1371/journal.pone.0118475reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Ciencia e Innovación https://doi.org/10.13039/501100004837 BFU2009-12410/BMCMinisterio de Ciencia e Innovación https://doi.org/10.13039/501100004837 BFU2010-17537European Commission https://doi.org/10.13039/501100000780 316137open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/3.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1548132026-06-06T12:50:31Z
dc.title.none.fl_str_mv GSK3β inhibition promotes synaptogenesis in Drosophila and mammalian neurons
title GSK3β inhibition promotes synaptogenesis in Drosophila and mammalian neurons
spellingShingle GSK3β inhibition promotes synaptogenesis in Drosophila and mammalian neurons
Cuesto, Germán
Synapses
Neurons
Drosophila melanogaster
Phosphorylation
Neuronal dendrites
Cell signaling
Larvae
Serine
title_short GSK3β inhibition promotes synaptogenesis in Drosophila and mammalian neurons
title_full GSK3β inhibition promotes synaptogenesis in Drosophila and mammalian neurons
title_fullStr GSK3β inhibition promotes synaptogenesis in Drosophila and mammalian neurons
title_full_unstemmed GSK3β inhibition promotes synaptogenesis in Drosophila and mammalian neurons
title_sort GSK3β inhibition promotes synaptogenesis in Drosophila and mammalian neurons
dc.creator.none.fl_str_mv Cuesto, Germán
Jordán-Álvarez, Sheila
Enríquez-Barreto, Lilian
Ferrús, Alberto
Morales, Miguel
Acebes, Ángel
author Cuesto, Germán
author_facet Cuesto, Germán
Jordán-Álvarez, Sheila
Enríquez-Barreto, Lilian
Ferrús, Alberto
Morales, Miguel
Acebes, Ángel
author_role author
author2 Jordán-Álvarez, Sheila
Enríquez-Barreto, Lilian
Ferrús, Alberto
Morales, Miguel
Acebes, Ángel
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Synapses
Neurons
Drosophila melanogaster
Phosphorylation
Neuronal dendrites
Cell signaling
Larvae
Serine
topic Synapses
Neurons
Drosophila melanogaster
Phosphorylation
Neuronal dendrites
Cell signaling
Larvae
Serine
description The PI3K-dependent activation of AKT results in the inhibition of GSK3β in most signaling pathways. These kinases regulate multiple neuronal processes including the control of synapse number as shown for Drosophila and rodents. Alzheimer disease's patients exhibit high levels of circulating GSK3β and, consequently, pharmacological strategies based on GSK3β antagonists have been designed. The approach, however, has yielded inconclusive results so far. Here, we carried out a comparative study in Drosophila and rats addressing the role of GSK3β in synaptogenesis. In flies, the genetic inhibition of the shaggy-encoded GSK3β increases the number of synapses, while its upregulation leads to synapse loss. Likewise, in three weeks cultured rat hippocampal neurons, the pharmacological inhibition of GSK3β increases synapse density and Synapsin expression. However, experiments on younger cultures (12 days) yielded an opposite effect, a reduction of synapse density. This unexpected finding seems to unveil an age- and dosage-dependent differential response of mammalian neurons to the stimulation/inhibition of GSK3β, a feature that must be considered in the context of human adult neurogenesis and pharmacological treatments for Alzheimer's disease based on GSK3β antagonists.
publishDate 2015
dc.date.none.fl_str_mv 2
2015-01-01
2015
2015-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/154813
https://dx.doi.org/urn:doi:10.1371/journal.pone.0118475
url https://ddd.uab.cat/record/154813
https://dx.doi.org/urn:doi:10.1371/journal.pone.0118475
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 BFU2009-12410/BMC
Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 BFU2010-17537
European Commission https://doi.org/10.13039/501100000780 316137
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/3.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/3.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300724

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