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

Abstract

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 Ca 21 -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 [Ca 21 ] 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 Ca 21 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.

Mechanisms of noise-induced hearing loss indicate multiple methods of prevention

“…Consistent with this, ebselen, which is an efficient scavenger of peroxynitrite as well as a gluthione peroxidase mimic, prevented noise-induced swelling of the auditory nerve dendrites (Yamasoba et al, 2005). Antioxidants also reduce glutamate-induced toxicity in other neural systems (Matteucci et al, 2005;Tastekin et al, 2005;Ibarretxe et al, 2006).…”

Morin exerts neuroprotective actions in Parkinson disease models in vitro and in vivo

“…Thus, we propose that morin maintains nigrostriatal pathway function by enhancing the survival of dopaminergic neurons in MPTP-lesioned mice. Besides the antioxidant activity that we detected in the in vitro model, the anti-inflammatory activity of morin may also contribute to its neuroprotective effects in vivo [12,31] . In conclusion, the present study indicates that morin has robust neuroprotective properties.…”

“…Morin (3,5,7,2',4'-pentahydroxyflavone, Figure 1) is a natural bioflavonoid that was originally isolated from members of the Moraceae family and is a constituent of many herbs, fruits and wine. Previous studies have shown that morin exerts antioxidant, anti-inflammatory, and antiproliferative effects in vivo and in vitro [11][12][13] . Studies investigating the neuroprotective effects of morin have been inconclusive.…”

Morin (3,5,7,2′,4′-Pentahydroxyflavone) Exhibits Potent Inhibitory Actions on Urate Transport by the Human Urate Anion Transporter (hURAT1) Expressed in Human Embryonic Kidney Cells

“…In fact, within the concentration range of the compound used, there was no observed toxicity on the cultured cells as indicated by initial studies of the compound by cell viability assays. Also, morin has been used on other cultured cells and no cytotoxic effects have been reported (Wu et al, 1994;Zeng et al, 1998;Mazzio et al, 2001;Ibarretxe et al, 2006). As for the three positive controls, they all showed inhibitory actions in the uptake assay.…”