Synaptic Failure and Adenosine Triphosphate Imbalance Induced by Amyloid-β Aggregates Are Prevented by Blueberry-Enriched Polyphenols Extract

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-beta peptide (A beta). Chronic treatment with A beta drastically reduced synaptic transmission and the extent of secretory vesicles, which were recovered partially with BB-4. Also, the extract recovered Ca2+ transients in hippocampal neurons preincubated with A beta (0.5 and 5 mu M) by about 25% +/- 3% and 30% +/- 2, respectively. In this work, we demonstrate a novel effect of the BB-4 extract on A beta-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 A beta. The present results strongly indicate that BB-4 plays a role in the process of A beta aggregation by reducing the toxic species (i.e., 40 kDa). These findings suggest that a blueberry extract can protect neuronal tissue from A beta 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. (C) 2011 Wiley-Liss, Inc.