GSK3β inhibition promotes synaptogenesis in Drosophila and mammalian neurons
Cuesto, Germán (Centro de Investigación Biomédica de La Rioja (Logronyo))
Jordán-Álvarez, Sheila (Instituto Cajal (Consejo Superior de Investigaciones Científicas))
Enríquez-Barreto, Lilian (Centro de Investigación Biomédica de La Rioja (Logronyo))
Ferrús, Alberto (Instituto Cajal (Consejo Superior de Investigaciones Científicas))
Morales, Miguel (Centro de Investigación Biomédica de La Rioja (Logronyo))
Acebes, Ángel (Instituto Cajal (Consejo Superior de Investigaciones Científicas))

Date:	2015
Abstract:	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.
Grants:	Ministerio de Ciencia e Innovación BFU2009-12410/BMC Ministerio de Ciencia e Innovación BFU2010-17537 European Commission 316137
Note:	Actualment, Lilian Enríquez-Barreto desenvolupa la seva recerca a l'Institut de Neurociències de la Universitat Autònoma de Barcelona
Rights:	Aquest 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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Synapses ; Neurons ; Drosophila melanogaster ; Phosphorylation ; Neuronal dendrites ; Cell signaling ; Larvae ; Serine
Published in:	PloS one, Vol. 10 Núm. 3 (March 2015) , e0118475, ISSN 1932-6203

DOI: 10.1371/journal.pone.0118475
PMID: 25764078

24 p, 5.5 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles