PMID- 28701919 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1662-5099 (Print) IS - 1662-5099 (Electronic) IS - 1662-5099 (Linking) VI - 10 DP - 2017 TI - Amyloid-beta Impairs Vesicular Secretion in Neuronal and Astrocyte Peptidergic Transmission. PG - 202 LID - 10.3389/fnmol.2017.00202 [doi] LID - 202 AB - Regulated secretion of neuropeptides and neurotrophic factors critically modulates function and plasticity of synapses and circuitries. It is believed that rising amyloid-beta (Abeta) concentrations, synaptic dysfunction and network disorganization underlie early phases of Alzheimer's disease (AD). Here, we analyze the impact of soluble Abeta(1-42) 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, Abeta(1-42), but not scrambled Abeta(1-42), dramatically impairs basal and Ca(2+)-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 Abeta(1-42) administration, whereas glutamate release from synaptic vesicle (SVs) remains unchanged. In agreement with cell culture results, Abeta(1-42) 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 Abeta in vitro and in situ. Furthermore, Abeta-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. FAU - Pla, Virginia AU - Pla V AD - Department of Cell Biology, Physiology and Immunology, University of BarcelonaBarcelona, Spain. AD - Institute of Neurosciences, University of BarcelonaBarcelona, Spain. FAU - Barranco, Neus AU - Barranco N AD - Department of Cell Biology, Physiology and Immunology, University of BarcelonaBarcelona, Spain. AD - Institute of Neurosciences, University of BarcelonaBarcelona, Spain. FAU - Pozas, Esther AU - Pozas E AD - Department of Cell Biology, Physiology and Immunology, University of BarcelonaBarcelona, Spain. FAU - Aguado, Fernando AU - Aguado F AD - Department of Cell Biology, Physiology and Immunology, University of BarcelonaBarcelona, Spain. AD - Institute of Neurosciences, University of BarcelonaBarcelona, Spain. LA - eng PT - Journal Article DEP - 20170628 PL - Switzerland TA - Front Mol Neurosci JT - Frontiers in molecular neuroscience JID - 101477914 PMC - PMC5487408 OTO - NOTNLM OT - Alzheimer's disease OT - BDNF OT - cerebral cortex OT - dense-core vesicles OT - exocytosis EDAT- 2017/07/14 06:00 MHDA- 2017/07/14 06:01 PMCR- 2017/01/01 CRDT- 2017/07/14 06:00 PHST- 2017/04/25 00:00 [received] PHST- 2017/06/08 00:00 [accepted] PHST- 2017/07/14 06:00 [entrez] PHST- 2017/07/14 06:00 [pubmed] PHST- 2017/07/14 06:01 [medline] PHST- 2017/01/01 00:00 [pmc-release] AID - 10.3389/fnmol.2017.00202 [doi] PST - epublish SO - Front Mol Neurosci. 2017 Jun 28;10:202. doi: 10.3389/fnmol.2017.00202. eCollection 2017.