Synaptic silencing and plasma membrane dyshomeostasis induced by amyloid-β 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-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.
Laboratorio de Screening de Compuestos Neuroactivos, Universidad de Concepción, Concepción, Chile. jorgefuentealba@udec.cl
Jorge
J
Fuentealba
Andrea
A
Dibarrart
Francisco
F
Saez-Orellana
María Cecilia
MC
Fuentes-Fuentes
Carlos N
CN
Oyanedel
José
J
Guzmán
Claudia
C
Perez
José
J
Becerra
Luis G
LG
Aguayo
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D045467:Elaeocarpaceae; D005260:Female; D005638:Fruit; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D016716:PC12 Cells; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010936:Plant Extracts