Oxidative stress mediated by NMDA, AMPA/KA channels in acute hippocampal slices: Neuroprotective effect of resveratrol

Abstract

Glutamate is the major excitatory neurotransmitter in the brain and over-stimulation of the glutamate receptors, NMDA, AMPA and kainate (KA), may cause neuronal death in epilepsy, seizures and neurodegenerative diseases. Mitochondria have critical cellular functions that influence neuronal excitability, such as regulation of Ca(2+) homeostasis and ATP production to maintain Na(+)K(+)-ATPase in the central nervous system (CNS). However, mitochondria are also the primary site of reactive oxygen species (ROS) production, and oxidative stress can induce cellular damage. Resveratrol, a polyphenol found in grapes and wines, presents antioxidant and neuroprotective effects on brain pathologies. This study sought to determine the neuroprotective effect of resveratrol against glutamate toxicity in acute hippocampal slices, using specific inhibitors of glutamate channels, and to investigate the targets of glutamate excitotoxicity, such as mitochondrial membrane potential (ΔΨ(m)), Na(+)K(+)-ATPase and glutamine synthetase (GS) activity. Resveratrol decreases intracellular ROS production, most likely by mechanisms involving NMDA, AMPA/KA, intracellular Ca(2+) and the heme oxygenase 1 (HO1) pathway, and prevents mitochondrial dysfunction and impairments in Na(+)K(+)-ATPase and GS activity after glutamate activation. Taken together, these results show that resveratrol may exhibit an important neuroprotective mechanism against neuropsychiatric disorders, focusing on mitochondrial bioenergetics and oxidative stress, as well as inhibitory effects on ionic channels.

Methylglyoxal and carboxyethyllysine reduce glutamate uptake and S100B secretion in the hippocampus independently of RAGE activation

“…# Significantly different from all groups. b S100B secretion-*significantly different from control and AG (0.25, 0.5 and 1 mM) Volterra and Meldolesi 2005;Nardin et al 2009;Quincozes-Santos et al 2014;Takano et al 2014). Furthermore, studies that have evaluated the methylglyoxal-induced changes in cultures of neurons or neuroblastoma have shown that these cells have a high susceptibility to damage caused by MG (De Arriba et al 2006;Di Loreto et al 2008).…”

Promising role of Carob (Ceratonia siliqua L) phytochemical components against neurotoxicity induced by monosodium glutamate

“…Also, it is the primary site of reactive oxygen species production enhancing cell damage and causing oxidative stress. Resveratrol was found to decrease intracellular ROS production, through NMDA, AMPA/KA, intracellular Ca(2+) and the heme oxygenase 1 (HO1) pathway [117].…”

Antioxidant therapies in traumatic brain injury: a review

“…The nuclear factorerythroid-2-related factor 2 (Nrf2) regulates HO1 transcription, which acts as a scavenger of NO and an inhibitor of iNOS. It has been reported that resveratrol modulates HO1 and iNOS expression in glial cells, so HO1 can also be critical to signaling the antioxidant response of resveratrol (54).…”