Differential oxidative stress in oligodendrocytes and neurons after excitotoxic insults and protection by natural polyphenols

• Published in: Glia 2006-01, Vol.53 (2), p.201-211
• Main Authors: Ibarretxe, Gaskon, Sánchez-Gómez, María Victoria, Campos-Esparza, María Rosario, Alberdi, Elena, Matute, Carlos
• Format: Article
• Language: English
• Subjects: AMPA receptor; Animals; Antioxidants - pharmacology; Biological and medical sciences; calcium; Calcium - metabolism; Caspase 3; Caspases - metabolism; Cell Survival - drug effects; Cytosol - drug effects; Cytosol - metabolism; excitotoxicity; Flavonoids - pharmacology; Free Radical Scavengers - pharmacology; free radicals; Fundamental and applied biological sciences. Psychology; Isolated neuron and nerve. Neuroglia; kainate receptor; mangiferin; Mitochondria - drug effects; Mitochondria - metabolism; mitochondrion; morin; Neurons - drug effects; Neuroprotective Agents; Neurotoxins - antagonists & inhibitors; Neurotoxins - toxicity; Oligodendroglia - drug effects; Optic Nerve - cytology; Optic Nerve - drug effects; Oxidative Stress - drug effects; Phenols - pharmacology; polyphenol; Polyphenols; Rats; Rats, Sprague-Dawley; reactive oxygen species; Reactive Oxygen Species - metabolism; Receptors, AMPA - drug effects; Receptors, Kainic Acid - drug effects; Vertebrates: nervous system and sense organs; Xanthones - pharmacology
• ISSN: 0894-1491; 1098-1136
• DOI: 10.1002/glia.20267

Oligodendrocytes are vulnerable to overactivation of both their AMPA receptors and their high‐ and low‐affinity kainate receptors. Depending on the intensity of the insult and the type of receptor activated, excitotoxic oligodendrocyte death mediated by these receptors has different characteristics. One important consequence at a cellular level is the ensuing oxidative stress, related to Ca2+‐dependent alterations in mitochondrial functioning. We observed that oxidative stress associated with selective AMPA receptor activation is much higher than that associated with the selective activation of high‐ and low‐affinity kainate receptors. Moreover, excitotoxic insults generate more intense oxidative stress in oligodendrocytes than in cortical neurons, though similar alterations in [Ca2+]i and mitochondrial potential were observed in both cell types. Nanomolar concentrations of mangiferin and morin, two natural polyphenols with antioxidant properties, partially protect oligodendrocytes as well as cortical neurons from mild, but not intense, insults mediated by AMPA receptors. In addition to presenting oxygen radical scavenging activity, mangiferin and morin attenuate the intracellular Ca2+ overload subsequent to the activation of AMPA receptors, a mechanism that may contribute to their protective properties. The inclusion of these antioxidant agents in therapeutic strategies for the treatment of diseases in which oligodendrocyte as well as neuron loss occurs may prove to be beneficial. © 2005 Wiley‐Liss, Inc.