Differential oxidative stress in oligodendrocytes and neurons after excitotoxic insults and protection by natural polyphenols.
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.
Ibarretxe
Gaskon
G
Departamento de Neurociencias, Facultad de Medicina y Odontologia, Universidad del País Vasco, Leioa, Spain.
Sánchez-Gómez
María Victoria
MV
Campos-Esparza
María Rosario
MR
Alberdi
Elena
E
Matute
Carlos
C
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D009836:Oligodendroglia / Q000187:drug effects*; D009900:Optic Nerve / Q000166:cytology / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D018091:Receptors, AMPA / Q000187:drug effects; D018092:Kainic Acid Receptors / Q000187:drug effects; D044004:Xanthones / Q000494:pharmacology; D047309:Flavones
D000975:Antioxidants; D002118:Calcium; D053148:Caspase 3; D020169:Caspases; D005419:Flavonoids; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D009498:Neurotoxins; D010636:Phenols; D059808:Polyphenols; D017382:Reactive Oxygen Species; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D044004:Xanthones; C013592:mangiferin; C008548:morin; D047309:Flavones; C505410:Casp3 protein, rat