Synaptic failure and adenosine triphosphate imbalance induced by amyloid-ß 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-ß peptide (Aß). Chronic treatment with Aß 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 Aß (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 Aß-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 Aß. The present results strongly indicate that BB-4 plays a role in the process of Aß aggregation by reducing the toxic species (i.e., 40 kDa). These findings suggest that a blueberry extract can protect neuronal tissue from Aß 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.

Synaptic silencing and plasma membrane dyshomeostasis induced by amyloid-ß peptide are prevented by Aristotelia chilensis enriched extract.

Alzheimer's disease (AD) is characterized by the presence of different types of extracellular and neurotoxic aggregates of amyloid-ß (Aß). Recently, bioactive compounds extracted from natural sources showing neuroprotective properties have become of interest in brain neurodegeneration. We have purified, characterized, and evaluated the protective potential of one extract enriched in polyphenols obtained from Aristotelia chilensis (MQ), a Chilean berry fruit, in neuronal models of AD induced by soluble oligomers of Aß1-40. For example, using primary hippocampal cultures from rats (E18), we observed neuroprotection when the neurons were co-incubated with Aß (0.5 µM) plus MQ for 24 h (Aß = 23 ± 2%; Aß + MQ = 3 ± 1%; n = 3). In parallel, co-incubation of Aß with MQ recovered the frequency of Ca2+ transient oscillations when compared to neurons treated with Aß alone (Aß = 72 ± 3%; Aß + MQ = 86 ± 2%; n = 5), correlating with the changes observed in spontaneous synaptic activity. Additionally, MAP-2 immunostaining showed a preservation of the dendritic tree, suggesting that the toxic effect of Aß is prevented in the presence of MQ. A new complex mechanism is proposed by which MQ induces neuroprotective effects including antioxidant properties, modulation of cell survival pathways, and/or direct interaction with the Aß aggregates. Our results suggest that MQ induces changes in the aggregation kinetics of Aß producing variations in the nucleation phase (Aß: k1 = 2.7 ± 0.4 × 10-3 s-1 MQ: k1 = 8.3 ± 0.6 × 10-3 s-1) and altering Thioflavin T insertion in ß-sheets. In conclusion, MQ induces a potent neuroprotection by direct interaction with the Aß aggregates, generating far less toxic species and in this way protecting the neuronal network.