Buchumschlag

Amyloid-beta mediates homeostatic synaptic plasticity

The physiological role of the amyloid-precursor protein (APP) is insufficiently understood. Recent work has implicated APP in the regulation of synaptic plasticity. Substantial evidence exists for a role of APP and its secreted ectodomain APPsα in Hebbian plasticity. Here, we addressed the relevance...

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Hauptverfasser: Galanis, Christos (VerfasserIn) , Fellenz, Meike (VerfasserIn) , Becker, Denise (VerfasserIn) , Bold, Charlotte (VerfasserIn) , Lichtenthaler, Stefan (VerfasserIn) , Müller, Ulrike C. (VerfasserIn) , Deller, Thomas (VerfasserIn) , Vlachos, Andreas (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: June 16, 2021
In: The journal of neuroscience
Year: 2021, Jahrgang: 41, Heft: 24, Pages: 5157-5172
ISSN:1529-2401
DOI:10.1523/JNEUROSCI.1820-20.2021
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1523/JNEUROSCI.1820-20.2021
Verlag, lizenzpflichtig, Volltext: https://www.jneurosci.org/content/41/24/5157
Volltext
Verfasserangaben:Christos Galanis, Meike Fellenz, Denise Becker, Charlotte Bold, Stefan F. Lichtenthaler, Ulrike C. Müller, Thomas Deller, and Andreas Vlachos
Beschreibung
Zusammenfassung:The physiological role of the amyloid-precursor protein (APP) is insufficiently understood. Recent work has implicated APP in the regulation of synaptic plasticity. Substantial evidence exists for a role of APP and its secreted ectodomain APPsα in Hebbian plasticity. Here, we addressed the relevance of APP in homeostatic synaptic plasticity using organotypic tissue cultures prepared from APP−/− mice of both sexes. In the absence of APP, dentate granule cells failed to strengthen their excitatory synapses homeostatically. Homeostatic plasticity is rescued by amyloid-β and not by APPsα, and it is neither observed in APP+/+ tissue treated with β- or γ-secretase inhibitors nor in synaptopodin-deficient cultures lacking the Ca2+-dependent molecular machinery of the spine apparatus. Together, these results suggest a role of APP processing via the amyloidogenic pathway in homeostatic synaptic plasticity, representing a function of relevance for brain physiology as well as for brain states associated with increased amyloid-β levels.
Beschreibung:Gesehen am 18.08.2021
Beschreibung:Online Resource
ISSN:1529-2401
DOI:10.1523/JNEUROSCI.1820-20.2021

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