Amb motiu del tancament d'estiu, la validació de documents es reprendrà a partir del 28 d'agost de 2026. Disculpeu les molèsties.
Con motivo del cierre de verano, la validación de documentos se reanudará a partir del 28 de agosto de 2026. Disculpad las molestias
Due to the summer closure, document validation will resume starting August 28, 2026. We apologize for any inconvenience.

Files

677148.pdf (4.57 MB)

Document type

Article

Version

Published version

Publication date

2017-06-28

Publication license

cc-by (c) Plá, Virginia et al., 2017
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/138658

Amyloid-β impairs vesicular secretion in neuronal and astrocyte peptidergic transmission

Journal Title

Authors

Director/Tutor

Journal ISSN

Volume Title

Related resource

https://doi.org/10.3389/fnmol.2017.00202

Abstract

Regulated secretion of neuropeptides and neurotrophic factors critically modulates function and plasticity of synapses and circuitries. It is believed that rising amyloid-β (Aβ) concentrations, synaptic dysfunction and network disorganization underlie early phases of Alzheimer's disease (AD). Here, we analyze the impact of soluble Aβ1-42 assemblies on peptidergic secretion in cortical neurons and astrocytes. We show that neurons and astrocytes differentially produce and release carboxypeptidase E (CPE) and secretogranin III (SgIII), two dense-core vesicle (DCV) markers belonging to the regulated secretory pathway. Importantly, Aβ1-42, but not scrambled Aβ1-42, dramatically impairs basal and Ca2+-regulated secretions of endogenously produced CPE and SgIII in cultured neurons and astrocytes. Additionally, KCl-evoked secretion of the DCV cargo brain-derived neurotrophic factor (BDNF) is lowered by Aβ1-42 administration, whereas glutamate release from synaptic vesicle (SVs) remains unchanged. In agreement with cell culture results, Aβ1-42 effects on CPE and SgIII secretion are faithfully recapitulated in acute adult brain slices. These results demonstrate that neuronal and astrocyte secretion of DCV cargos is impaired by Aβ in vitro and in situ. Furthermore, Aβ-induced dysregulated peptidergic transmission could have an important role in the pathogenesis of AD and DCV cargos are possible candidates as cerebrospinal fluid (CSF) biomarkers.

Subject

Malaltia d'Alzheimer, Escorça cerebral

Subject (English)

Alzheimer's disease, Cerebral cortex

Citation

Collections

Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)

Citation

PLÁ, Virginia, et al. Amyloid-β impairs vesicular secretion in neuronal and astrocyte peptidergic transmission. Frontiers In Molecular Neuroscience. 2017. Vol. 10, num. 202. ISSN 1662-5099. [consulted: 19 of August of 2026]. Available at: https://hdl.handle.net/2445/138658

Export metadata

JSON - METS

Share record