Quercetin Exerts Differential Neuroprotective Effects Against H2O2 and Aβ Aggregates in Hippocampal Neurons: the Role of Mitochondria

• Published in: Molecular neurobiology 2017-11, Vol.54 (9), p.7116-7128
• Main Authors: Godoy, Juan A., Lindsay, Carolina B., Quintanilla, Rodrigo A., Carvajal, Francisco J., Cerpa, Waldo, Inestrosa, Nibaldo C.
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Antioxidants; Biomedical and Life Sciences; Biomedicine; Calcium; Calcium homeostasis; Cell Biology; Cell death; Deregulation; Hippocampus; Homeostasis; Hydrogen peroxide; Mitochondria; Molecular modelling; Neurobiology; Neurodegeneration; Neurodegenerative diseases; Neurology; Neurons; Neuroprotection; Neurosciences; Neurotoxicity; Oxidative stress; Pathogenesis; Quercetin; Reactive oxygen species; Superoxide; Toxicity; β-Amyloid
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-016-0203-x

Amyloid-β peptide (Aβ) is one of the major players in the pathogenesis of Alzheimer’s disease (AD). Despite numerous studies, the mechanisms by which Aβ induces neurodegeneration are not completely understood. Oxidative stress is considered a major contributor to the pathogenesis of AD, and accumulating evidence indicates that high levels of reactive oxygen species (ROS) are involved in Aβ-induced neurodegeneration. Moreover, Aβ can induce the deregulation of calcium homeostasis, which also affects mitochondrial function and triggers neuronal cell death. In the present study, we analyzed the effects of quercetin, a plant flavonoid with antioxidant properties, on oxidative stress- and Aβ-induced degeneration. Our results indicate that quercetin efficiently protected against H 2 O 2 -induced neuronal toxicity; however, this protection was only partial in rat hippocampal neurons that were treated with Aβ. Treatment with quercetin decreased ROS levels, recovered the normal morphology of mitochondria, and prevented mitochondrial dysfunction in neurons that were treated with H 2 O 2 . By contrast, quercetin treatment partially rescued hippocampal neurons from Aβ-induced mitochondrial injury. Most importantly, quercetin treatment prevented the toxic effects that are induced by H 2 O 2 in hippocampal neurons and, to a lesser extent, the Aβ-induced toxicity that is associated with the superoxide anion, which is a precursor of ROS production in mitochondria. Collectively, these results indicate that quercetin exerts differential effects on the prevention of H 2 O 2 - and Aβ-induced neurotoxicity in hippocampal neurons and may be a powerful tool for dissecting the molecular mechanisms underlying Aβ neurotoxicity.