Synaptic Silencing and Plasma Membrane Dyshomeostasis Induced by Amyloid-β Peptide are Prevented by Aristotelia chilensis Enriched Extract

Abstract

Alzheimer's disease (AD) is characterized by the presence of different types of extracellular and neurotoxic aggregates of amyloid-β (Aβ). 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 Aβ1-40. For example, using primary hippocampal cultures from rats (E18), we observed neuroprotection when the neurons were co-incubated with Aβ (0.5 μM) plus MQ for 24 h (Aβ = 23 ± 2%; Aβ + MQ = 3 ± 1%; n = 3). In parallel, co-incubation of Aβ with MQ recovered the frequency of Ca2+ transient oscillations when compared to neurons treated with Aβ alone (Aβ = 72 ± 3%; Aβ + 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 Aβ 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 Aβ aggregates. Our results suggest that MQ induces changes in the aggregation kinetics of Aβ producing variations in the nucleation phase (Aβ: 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 β-sheets. In conclusion, MQ induces a potent neuroprotection by direct interaction with the Aβ aggregates, generating far less toxic species and in this way protecting the neuronal network.

Amyloid Beta-Protein and Neural Network Dysfunction

“…Using this approach, it has been found that medial septal neurons lose their theta firing coherence upon A β application [ 66 ]. This effect has been evaluated in cultured neurons that exhibit synchronous spontaneous calcium transients [ 67 – 70 ], showing that either increasing A β production by transfecting the cultures with the human APP gene [ 69 ] or by directly applying A β to the culture medium drastically reduced the synchronized neuronal calcium oscillations [ 67 , 68 , 70 ]. Recently, calcium imaging has also been used in vivo to evaluate neural activity, either in the hippocampal CA1 region or in the cortex of the double transgenic mice expressing APPswe and mutated presenilin 1 (G384A) [ 30 , 31 ].…”

Stevia vs. Sucrose: Influence on the Phytochemical Content of a Citrus–Maqui Beverage—A Shelf Life Study

“…Actually, the nutritional and phytochemical characterization of this fruit, as well as its biological properties, have suggested the capacity of maqui anthocyanins to modulate hyperglycemia and insulin sensitivity [4] as well as to inhibit mechanisms involved in the absorption of sugars [5]. Moreover, other phenolic compounds present in maqui are also responsible for the high antioxidant capacity and the ability to inhibit adipogenesis and inflammation [16,17], thus decreasing oxidative stress and providing cardioprotective and neuroprotective effects [18][19][20].…”

Determination of polyphenolic profile, antioxidant activity and antibacterial properties of maqui [Aristotelia chilensis (Molina) Stuntz] a Chilean blackberry

“…These compounds are responsible of their intense blackish colour and the major contributor to their antioxidant potential, which is one of the highest among known berry fruits of the entire world. 12 Many studies have linked anthocyanins content in maqui berry with its wide biological activities such as anti-diabetic effects, 13 prevention of Alzheimer's disease, 14 inhibition of adipogenesis and inflammation, 10 prevention against oxidative stress 15 and prevention of low-density lipoprotein oxidation. 12 Whilst there are several works, in the scientific literature, reporting the biological effects and the anthocyanins contents of berry fruits in general and maqui berry in particular, there is lack of information regarding the phenolic acids and flavonoids presents in this fruit.…”