title: Synaptic failure and adenosine triphosphate imbalance induced by amyloid-β aggregates are prevented by blueberry-enriched polyphenols extract.
abstract: The potential neuroprotective properties of fruits have been widely recognized. In this study, we evaluated the protective properties of a blueberry extract (BB-4), rich in polyphenols, in a neurodegenerative model induced by amyloid-β peptide (Aβ). Chronic treatment with Aβ drastically reduced synaptic transmission and the extent of secretory vesicles, which were recovered partially with BB-4. Also, the extract recovered Ca(2+) transients in hippocampal neurons preincubated with Aβ (0.5 and 5 μM) by about 25% ± 3% and 30% ± 2, respectively. In this work, we demonstrate a novel effect of the BB-4 extract on Aβ-induced ATP leakage, in which this extract was able to antagonize the acute ATP leakage but not chronic ATP depletion. On the other hand, BB-4 prevented the uncoupling of mitochondrial function induced by FCCP by about 85%, but it was unable to modify the uncoupling induced by Aβ. The present results strongly indicate that BB-4 plays a role in the process of Aβ aggregation by reducing the toxic species (i.e., 40 kDa). These findings suggest that a blueberry extract can protect neuronal tissue from Aβ toxicity mainly through its antiaggregation property, and its antioxidant properties and mitochondrial membrane potential capacities are secondary mechanisms important in chronic stages. Our work suggests that BB-4 could be an important nutritional complement to neuronal health as well as a potential nutraceutical formulation useful as a dietary supplement in the elderly.
authors.affiliation: Neuroactive Drugs Screening Unit, Department of Physiology, Faculty of Biological Sciences, University of Concepción, Concepcion, Chile. jorgefuentealba@udec.cl
authors.forename: Jorge
authors.initials: J
authors.lastname: Fuentealba
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Dibarrart
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: Fuentes-Fuentes
authors.forename: Francisco
authors.initials: F
authors.lastname: Saez-Orellana
authors.forename: Karin
authors.initials: K
authors.lastname: Quiñones
authors.forename: Leonardo
authors.initials: L
authors.lastname: Guzmán
authors.forename: Claudia
authors.initials: C
authors.lastname: Perez
authors.forename: Jose
authors.initials: J
authors.lastname: Becerra
authors.forename: Luis G
authors.initials: LG
authors.lastname: Aguayo
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000009:adverse effects*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D029798:Blueberry Plants; D002460:Cell Line; D005638:Fruit; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D016716:PC12 Cells; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D018696:Neuroprotective Agents; D010936:Plant Extracts; D059808:Polyphenols; D000255:Adenosine Triphosphate